Search PubMed⌕ Search

Biomedical subjects

V Carter

Publications and source records attributed to V Carter.

At least 19 recordsLinked to original sources
PubMed2001

CAMPATH-1M T-cell depleted BMT for SCID: long-term follow-up of 19 children treated 1987-98 in a single center.

BACKGROUND: SCID can be cured by BMT. Depletion of mature T cells from BM has enabled HLA non-identical stem-cell transplantation. We report the outcome of 30 patients treated with 37 T-cell depleted BMT procedures using CAMPATH-1M in vitro between 1987-98 in a single center. METHODS: Immune reconstitution and quality-of-life were assessed in 19 longterm survivors. All but two received pre-transplant conditioning. T- and B-cell chimerism, numbers and function were analyzed during a median follow-up of 5.3 years (range 1.33-12). RESULTS: The overall engraftment rate was 59%, six children required repeated BMT and the survival rate was 63%. All have donor T cells, 58% normal T-cell numbers and 74% normal T-cell function. Of 17 evaluated, 16 patients (94%) have normal IgM and IgG levels, and production of specific Abs to protein Ags, but only 5/16 (31%) have a good response to pneumococcal polysaccharide. Early and late post-BMT complications were rare and there were no delayed deaths. Only one child continues on long-term i.v. Ig 4-years post-BMT. Eleven children died (37%). DISCUSSION: CAMPATH-1M T-cell depleted BMT for SCID resulted in 63% survival. Deaths of 11 children were mainly due to pre-existing infections. Seventeen of 19 long-term survivors have normal immune function and good quality-of-life.

Alemtuzumab↗
PubMed2000

The relevance of donor T cell-directed immunoglobulin G in historic sera in the age of flow cytometry.

BACKGROUND: Renal transplant recipients with a positive historic cross-match due to donor T cell-directed IgG antibodies are considered to have decreased graft survival, even if their current serum is negative prior to transplantation. With the use of flow cytometric cross-match for testing current sera, false-negative results could be eliminated and the outcome of transplantation in this group of patients could be improved, assuming that immunological memory is effectively controlled with immunosuppression. METHODS: We reviewed our records to identify those patients who underwent cadaveric renal transplant, with a historic IgG positive cytotoxic T cell cross-match and a current negative flow cytometric T cell cross-match. RESULTS: Eighteen patients underwent cadaveric renal transplant in the face of a historic IgG positive T cell cross-match and a current negative flow cytometric T cell cross-match. In 14 patients treated with cyclosporine-based immunosuppression the 1-, 2-, and 3-year cumulative graft survival rates were 57, 50, and 43%, respectively. Ten of the 14 patients (71%) ultimately lost their grafts. CONCLUSIONS: Even with negative flow cytometric cross-match in current serum, a positive historic conventional cross-match suggests a high risk of graft failure.

Adolescent↗
PubMed2000

An HLB-B null allele (B*0808N) caused by a nucleotide deletion in exon 3, found in the family of a bone marrow transplant recipient.

We have identified a variant HLA-B allele, B*0808N, segregating through two generations of healthy individuals, whilst HLA typing the family of a bone marrow patient. Serological typing identified a disparity between the father (A1, A3 B7 DR7) and the brother (A1, A2 B56 DR1, DR7) of the patient. Low/medium resolution polymerase chain reaction using sequence-specific primers (PCR-SSP) revealed a B*08 allele undetectable by serological methods. High resolution DNA typing by polymerase chain reaction-sequencing based typing (PCR-SBT), revealed a nucleotide deletion at position 131 (C) in exon 3, the only difference between the new allele and B*0801. The deletion results in a frame shift in the protein coding sequence, introducing a premature termination codon (TGA) in exon 4. Although a B*08 allele is present in these individuals, the deletion prevents correct expression of the antigen on the cell surface.

Alleles↗
PubMed2000

Identification of an HLA-B7 serological variant and its characterization by sequencing based typing.

We have identified an HLA-B*07 variant allele, B*0716, in a Caucasoid cadaver kidney donor. The HLA class I type by polymerase chain reaction using sequence-specific primers (PCR-SSP) was A*01, 32; B*07, 08; Cw*07. Serological typing, using monoclonal and polyclonal anti-HLA antisera, gave disparate results for the B antigens. Monoclonal antibodies identified B7 and B8 antigens but polyclonal antisera recognised only the B8 antigen. PCR using sequencing based typing (PCR-SBT) confirmed the presence of both B*0703 and B*0801 alleles but with a mutation in one of the alleles. The HLA-B*07 allele was isolated by allele-specific PCR and was shown to have a mutation, G-->T, at 292 in exon 2. This mutation changes codon 74, which encodes aspartic acid (GAC) present in all previously identified B*07 alleles, to tyrosine (TAC) in the variant. The serological results suggest that codon 74 is a crucial part of a B7 antigen-specific epitope recognised by tissue typing polyclonal antisera.

Alleles↗
PubMed1998

Trypanosoma brucei: molecular cloning and stage-regulated expression of a malate dehydrogenase localized to the mitochondrion.

African trypanosomes exhibit dramatic developmental changes in carbohydrate and energy metabolism, with cytochrome-mediated respiration playing an important role only in the insect stages. The parasites possess three isozymes of malate dehydrogenase, each of which has a different subcellular localization and, likely, a distinct metabolic role. We have cloned and characterized a cDNA encoding one of these malate dehydrogenases. Epitope tagging and transfection experiments demonstrate that the corresponding protein is localized to the mitochondrion and that an intact amino terminus is required for proper compartmentalization. The abundance of transcript is developmentally regulated, with higher levels in procyclic stage parasites.

Amino Acid Sequence↗
PubMed1997

The effects of simulated Bier block IVRA on intracompartmental tissue pressure.

BACKGROUND: Intravenous regional anesthesia (IVRA) is a useful anesthetic method for closed reduction of fractures. However, IVRA has been associated with an increased incidence of compartment syndrome when treating tibial shaft fractures. The purpose of this study was to measure changes in anterior leg compartment pressures during simulated IVRA. METHODS: A volunteer study was performed. An indwelling catheter placed in a consistent location between subjects was used to measure tissue pressure. A vinyl leg splint was used for exsanguination followed by thigh tourniquet inflation (300 mmHg). Normal saline (1.5 mL/kg) was injected through the greater saphenous vein (1.0 mL/s). Pressure measurements were obtained before and after tourniquet inflation, at 10 mL increments during saline injection, and intermittently after volume injection with the tourniquet inflated, then deflated. RESULTS: There was no significant difference in tissue pressure before (2.4 +/- 2.2 mmHg) and after (4.3 +/- 3.7 mmHg) tourniquet inflation (P = 0.11). No significant difference in tissue pressure were found as a function of injected volume (P = 0.62), as a function of time following saline injection during tourniquet inflation (P = 0.08), and after tourniquet deflation (P = 0.16). CONCLUSIONS: We conclude that in the normal atraumatic limb, simulated IVRA using normal saline does not increase tissue pressure within the anterior leg compartment.

Adult↗
PubMed1996

A novel variant of the beta-subunit of the amiloride-sensitive sodium channel in African Americans.

The amiloride-sensitive sodium channel is responsible for the rate-limiting step of sodium reabsorption in the distal renal tubule, and thus may play a key role in the maintenance of sodium balance and blood pressure. In this study, a genetic variant that results in a change of threonine to methionine at amino acid 594 (T594 M) in the carboxy-terminus of the beta-subunit of the amiloride-sensitive sodium channel has been identified. This variant was present in 6.1% of African-American subjects (N = 231) but was not seen in Caucasians (N = 192). Whole cell voltage clamp of B-lymphocytes from individuals with the T594 M variant showed similar basal membrane slope conductance, compared with the wild-type but increased response to cAMP analog.

Aldosterone↗
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↗