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Biomedical subjects

V Carter

Publications and source records attributed to V Carter.

17 recordsLinked to original sources
PubMed1995

Trypanosoma congolense: developmental regulation of protein kinases and tyrosine phosphorylation during the life cycle.

In higher eukaryotes, key steps in the control of growth and proliferation are regulated by protein phosphorylation. However, little is known about the role of protein phosphorylation in the developmental cycles of pathogenic protozoa. In Trypanosoma brucei, only the bloodform and procyclic form stages can be obtained in sufficient numbers for biochemical analyses. However, the entire life cycle of Trypanosoma congolense can be generated in vitro, providing sufficient material for analyses of the different developmental stages. The studies reported here provide a series of snapshots documenting the activity of a number of protein serine/threonine kinases and the pattern of tyrosine-phosphorylated proteins throughout the T. congolense developmental cycle. Metacyclic forms and mammalian bloodforms showed similar profiles of protein kinase activity, as did procyclic forms and epimastigotes. Most tyrosine-phosphorylated proteins were shared between all developmental stages, with the exception of a 100-kDa metacyclic-specific species. The developmental changes in molecules involved in protein phosphorylation in the different developmental stages support the concept that changes in protein phosphorylation networks are important correlates of the developmental process in African trypanosomes.

Animals↗
PubMed1994

Translational control mediates the developmental regulation of the Trypanosoma brucei Nrk protein kinase.

The expression and function of eukaryotic protein kinases is highly regulated, primarily through transcriptional and post-translational processes. In this report we demonstrate an unusual mechanism for controlling protein kinase function, translational control. The Trypanosoma brucei Nrk loci encode predicted protein kinases. Here we show that Nrk has protein serine-threonine kinase activity and examine the expression and activity of Nrk during parasite development. While Nrk transcripts were previously found to be constitutively expressed throughout the life cycle, we now find that expression of Nrk protein is highly stage-regulated. Immunoblot analysis revealed that Nrk expression dramatically increased as the parasites differentiated from proliferative slender bloodforms to the non-proliferative stumpy bloodforms. Procyclic form organisms expressed moderate levels of Nrk. Analysis of Nrk activity demonstrated that it too was highest in stumpy bloodforms. Metabolic labeling and pulse-chase analysis demonstrated that Nrk accumulation was highest in stumpy bloodforms and indicated that Nrk abundance is primarily controlled at the level of biosynthesis rather than turnover. All Nrk mRNA was contained in the poly(A)+ fraction, and the 5' ends of the transcript were the same in each developmental stage. Thus, Nrk is under translational control. The strict developmental regulation of the Nrk enzymes within the trypanosome life cycle suggests that the Nrk protein kinase may play a role in parasite differentiation.

Animals↗
PubMed1994

Radiographic diagnosis of ankle fractures: are three views necessary?

One hundred and twenty-three sets of emergency room ankle x-rays (anteroposterior lateral and mortise) were retrospectively reviewed to determine whether all three views were necessary to diagnose the presence of an ankle fracture. Four physicians (two orthopaedic surgeons, one musculoskeletal radiologist, and one emergency room physician) reviewed all randomly ordered sets of films twice--once with all three views and once with only the lateral and mortise views. The overall accuracy of two views was within the 95% expected threshold of accuracy using three views. The lateral and mortise views alone appear sufficient for ankle fracture diagnosis, and imply a substantial decrease in radiation and cost savings to the patient.

Ankle Injuries↗
PubMed1994

The protein phosphatase inhibitor okadaic acid induces defects in cytokinesis and organellar genome segregation in Trypanosoma brucei.

Mitosis and cytokinesis are events that are highly coordinated in most eukaryotic cell cycles. African trypanosomes possess a single mitochondrion and must additionally coordinate the organellar division cycle. Here we report that okadaic acid, a potent and specific inhibitor of protein phosphatases PP1and PP2A, uncouples these cycles in living trypanosomes. Cell cycle analysis of treated cells revealed elevated DNA content. Microscopic examination indicated that okadaic acid treatment yielded multinucleate cells with a single mitochondrial network indicating these cells have undergone mitosis but failed to complete cytokinesis. Immunofluorescence analysis of 5-bromo-2-deoxyuridine incorporation demonstrated that the mitochondrial DNA was replicated but did not segregate. The dose response curve for inhibition of the normal cell cycle paralleled that for the in vitro inhibition of protein phosphatase activities with IC50s of approximately 20 nM okadaic acid. These results suggest the involvement of a PP1/PP2A-like activity in coordinating mitosis, mitochondrial DNA division and cytokinesis in trypanosomes.

Animals↗
PubMed1994

Cell cycle-specific induction of an 89 kDa serine/threonine protein kinase activity in Trypanosoma brucei.

The cell cycle compartmentalization of specific activities of the protozoan parasite Trypanosoma brucei has remained unexplored due to the lack of a cell synchronization protocol. We report here that stationary phase cells stimulated to enter the cell cycle showed significant synchrony through the first cycle. The pattern of tyrosine phosphorylated proteins, known to undergo alterations during trypanosome development, showed only moderate changes as quiescent cells entered the cycle, particularly an increase in a 77 kDa species. However, the activity of an 89 kDa protein kinase (SPK89), previously demonstrated to be restricted to the proliferative stages of the parasite's life cycle, markedly increased as the population entered S phase. Cell sorting experiments demonstrated that SPK89 activity was highest in S phase cells and moderate in G2/M cells. The entry into S phase and increased SPK89 activity did not depend on serum factors but required protein synthesis for a discrete period after stimulation. Various modulators of protein phosphorylation were tested to determine their effects on progression to S and SPK89 activity. Only staurosporine and genistein were effective. However, both of these compounds inhibited virtually all protein phosphorylation and protein synthesis in the parasites. Thus these drugs cannot be used as specific protein kinase inhibitors in trypanosomes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Protein kinases in divergent eukaryotes: identification of protein kinase activities regulated during trypanosome development.

The role of protein kinases in organisms that diverged early in the eukaryotic lineage is relatively unexplored. In this study, we determined that primitive parasitic protozoa possess multiple protein-serine kinases and inferred the presence of protein-tyrosine kinases through sensitive immunoblotting techniques. To further explore the role of protein kinases in parasite development, we examined the activity of eight renaturable protein kinases during the life cycle of the protozoan parasite Trypanosoma brucei. The activities of six protein-serine/threonine kinases were regulated during development, with several distinct patterns of regulation. In addition, an 89-kDa protein kinase was detected in dividing cells but not in nondividing cells. Our data indicate that even the most primitive eukaryotes possess a large complement of protein kinases, including protein-tyrosine kinases as well as protein-serine/threonine kinases. The data further suggest that protein kinases may play a pivotal role in regulation of proliferation and differentiation in protozoa.

Animals↗
PubMed1993

Critical pathways--the pivotal tool.

Case management is a nursing model that hospital administrators have implemented in an effort to reduce costs and improve quality. The pivotal tool that case management utilizes to standardize treatment plans, trend deviations from the standard, and document care is the critical pathway. Proper development, implementation, and utilization of critical pathways provide health care professionals and administrators with quantitative data on correlations between effective resource utilization and patient outcomes.

Critical Care↗
PubMed1989

Significance of positive endocervical curettage in predicting endocervical canal involvement in patients with cervical intraepithelial neoplasia.

A total of 108 patients with positive endocervical curettage who underwent cone biopsy were carefully examined to determine the accuracy of endocervical curettage (ECC) in predicting endocervical canal involvement with cervical intraepithelial neoplasia (CIN). The data suggest a 63% correlation between positive ECC and endocervical canal involvement: 72.4% of patients with CIN III on cervical biopsy had endocervical canal involvement compared to 27.3% who had CIN I. Two patients with positive ECC were found to have invasive cancer on cone biopsy.

Adolescent↗
PubMed1989

Comparison of short and long thumb-spica casts for non-displaced fractures of the carpal scaphoid.

A prospective study was undertaken of fifty-one patients who were randomly assigned to treatment with either a long or a short thumb-spica cast for a non-displaced fracture of the carpal scaphoid. The duration of follow-up was at least until union; the average follow-up was twelve months. Twenty-eight fractures were treated with a long thumb-spica cast and twenty-three, with a short thumb-spica cast. The hands that initially were treated with a long thumb-spica cast were placed in a short thumb-spica cast after six weeks. Fractures that initially were treated with a long thumb-spica cast united at an average of 9.5 weeks and those that were maintained in a short thumb-spica cast, at an average of 12.7 weeks. There were no non-unions and two delayed unions in the fractures that initially were treated with a long thumb-spica cast, compared with two non-unions and six delayed unions in those that had only a short thumb-spica cast. Fractures of the proximal or middle third of the carpal scaphoid had a significantly shorter time to union when they were treated initially in a long thumb-spica cast. Fractures of the distal third did well regardless of the type of immobilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Chronobiological study of plasma exudation in carrageenan-paw oedema in the rat.

The time-courses of exudation of protein-bound Evans' blue and of the formation of oedema following the injection of carrageenan (2 mg) or normal saline in the rat hind paw at 10.00 hours and 21.00 hours were studied. During the first 90 min after the carrageenan injection, the tissue content of the dye and the oedema formed were much greater when the inflammatory agent was administered at 21.00 hours than at 10.00 hours. A second study carried out at every 3 hours of the 24 hour span showed the presence of a circadian rhythm in the exudation of protein in the paw and in the formation of oedema. The paw volume and content of the dye were found to be highest between 19.00 hours and 01.00 hours whereas the minimal values were obtained at 16.00 hours. There is a correlation between the exudation of plasma proteins and the formation of oedema.

Animals↗
PubMed1978

Pharmacokinetics and disposition of lidamidine hydrochloride (WHR-1142A), a novel antidiarrheal agent, in rat and monkey.

14C-Labelled 1-(2,6-dimethylphenyl)-3-methylamidinourea hydrochloride (14C-WHR-1142A, lidamidine hydrochloride) was rapidly and quantitatively absorbed from the gastrointestinal tract of rat and monkey after a single oral dose of 5 mg/kg (base). Peak 14C levels occurred within 30 min and the radiolabel was found in both the plasma and cellular components of whole blood. The half-life of the parent compound was 30 min in rat and 1 h in the monkey. The label was essentially cleared from all tissues examined within 24 h in the rat. In both rat and monkey, the compound was extensively metabolized (greater than 90%) prior to excretion and eliminated primarily in the urine (95% of the 14C dose could be accounted for in urine within 24 h in the monkey and 65% within 24 h in the rat); about 15-20% of the dose was recovered in feces within 24 h in the rat. In rat, a significant portion of the dose was eliminated in bile, and enterohepatic recirculation of 14C excreted in bile occurred. In contrast, biliary elimination of 14C was not a major pathway in the monkey.

Amidines↗
PubMedDate not supplied

Case management: the relationship between structure & environment.

In response to increasingly uncertain practice environments, case management structural dimensions of role differentiation, task coordination, and decentralization remained constant, while nurse participation in decision making increased significantly.

Decision Making, Organizational↗
PubMedDate not supplied

A cost-effectiveness analysis of acute care case management outcomes.

Case management was more cost effective in a moderately uncertain practice environment than in either a low or a high uncertainty environment. The environmental state, case manager role differentiation, and information coordination contributed most strongly to these outcomes.

Cost-Benefit Analysis↗
PubMedDate not supplied

Environmental uncertainty: implications for practice model redesign.

Analysis of one academic medical center revealed three distinct nursing practice environments distinguished by increasing levels of complexity, change, unpredictability, and uncertainty. Designing practice models to accommodate these conditions will facilitate more efficient and effective patient outcomes.

Academic Medical Centers↗