Search PubMed⌕ Search

Biomedical subjects

R E Ware

Publications and source records attributed to R E Ware.

At least 91 records · Page 5Linked to original sources
PubMed1993

Hemoglobin sickle-Lepore: report of two siblings and review of the literature.

Hemoglobin Lepore is composed of two normal alpha-globin chains and two delta-beta fusion globin chains that result from nonhomologous crossing over of genetic material during meiosis. The doubly heterozygous condition of sickle hemoglobin with Lepore hemoglobin (Hb S-Lepore) is rare, having been described previously in only nine patients. We report two siblings with Hb S-Lepore who have similar hematologic characteristics but a marked difference in clinical severity.

Child↗
PubMed1993

T cell CD7 mRNA expression is regulated by both transcriptional and post-transcriptional mechanisms.

The CD7 molecule is a 40 kDa member of the Ig superfamily that is acquired early in human T cell ontogeny. Because of the putative three-dimensional structure of CD7 and its presence on T cell precursors, it has been postulated that CD7 serves as an adhesion molecule that facilitates early T cell maturation. Ligand binding to CD7 on mature peripheral blood (PB) T cells has been reported to deliver a co-mitogenic signal with CD3 mAb for T cell triggering. In previous work, we found that CD7 was upregulated on PB T cells following a non-mitogenic ionomycin-induced transmembrane calcium flux, which induced new T cell CD7 transcription without affecting CD7 mRNA stability. In this report, we have studied the upregulation of CD7 expression on PB T cells following stimulation by ionomycin, phytohemagglutinin (PHA), and CD3 mAb. PHA prolonged T cell CD7 mRNA stability without affecting CD7 transcription, while stimulation of PB T cells with CD3 mAb both increased T cell CD7 transcription and prolonged CD7 mRNA stability. Experiments with cycloheximide demonstrated superinduction of T cell CD7 mRNA and showed that new protein synthesis was not required for ionomycin-induced upregulation of T cell CD7 expression. Cyclosporin A inhibited ionomycin-induced T cell CD7 upregulation at the level of CD7 mRNA transcription and elongation. These data demonstrate that ionomycin, PHA, and CD3 mAb act via different mechanisms to increase T cell CD7 expression, and that both transcriptional and post-transcriptional mechanisms are used to modify CD7 mRNA levels.

Antibodies, Monoclonal↗
PubMed1993

A human chimera for von Willebrand disease following bone marrow transplantation.

PURPOSE: von Willebrand disease (vWD) is a common bleeding disorder characterized by quantitative or qualitative defects in von Willebrand factor (vWF), a protein important for coagulation and platelet adhesion. There are two forms of vWF currently recognized: plasma vWF synthesized by endothelial cells and platelet vWF produced within megakaryocytes. Although both plasma and platelet vWF play important roles in overall hemostasis, the relative contribution of each form is not clear. PATIENTS AND METHODS: We report the results of bone marrow transplantation from a donor with Type I vWD into a hemostatically normal recipient. RESULTS: Following engraftment, the recipient appears to be a human chimera for vWD, with normal amounts of plasma vWF from endogenous endothelial cells, but low levels of platelet vWF derived from donor megakaryocytes. CONCLUSIONS: Although the vWD chimerism has not been associated with any clinical manifestations, the bleeding time has become prolonged, suggesting that platelet vWF is important for normalization of the bleeding time.

Adolescent↗
PubMed1992

Diagnosis and management of common bile duct stones in patients with sickle hemoglobinopathies.

Nine of 35 patients with sickle hemoglobinopathies and cholelithiasis were found to have concomitant common bile duct (CBD) stones. We describe the diagnosis and management of these patients with CBD stones. Historical information, physical examination, and routine laboratory tests were unable to identify accurately the patients with CBD stones. Similarly, ultrasonography of the hepatobiliary system was an insensitive method for detecting CBD stones, as only 3 of 8 patients were correctly identified. In contrast, both an intraoperative cholangiogram and endoscopic retrograde cholangiopancreatography were sensitive procedures for detection of CBD stones. We conclude that CBD stones are relatively common in patients with sickle cell disease and cholelithiasis, and clinicians should have a high index of suspicion for their presence.

Adolescent↗
PubMed1992

Laparoscopic cholecystectomy in young patients with sickle hemoglobinopathies.

Nine young patients with sickle hemoglobinopathies successfully underwent laparoscopic cholecystectomy; no complications resulted from the procedure. The mean postoperative hospital stay was 1.6 days. This technique appears to be a safe and efficacious procedure in children with sickle hemoglobinopathies who require cholecystectomy for cholelithiasis.

Adolescent↗
PubMed1992

Surgical management of children with hemoglobinopathies.

Sickle hemoglobinopathies include sickle cell disease, sickle-C disease, and sickle-beta thalassemia. Patients with these disorders commonly suffer a multitude of destructive events to vital organs, especially to the central nervous system, the spleen, the kidney, the lung, and the heart as a result of microvascular plugging by the sickled erythrocytes. Thoughtful preparation for anesthesia and operation, especially when directed by experienced individuals, can greatly reduce the hazard of inducing the sickle crises that formerly plagued individuals with sickle hemoglobinopathies who faced major operations under general anesthesia. The patient must be free of any acute illness, especially one involving the respiratory system. Adequate hydration preoperatively combined with avoiding perioperative hypoxia, hypothermia, and acidosis, the triggers for sickling, will go far toward avoiding sickle-induced complications. Modern transfusion therapy, consisting of multiple small transfusions of Hb A erythrocytes administered over several weeks prior to the operation, not only corrects the chronic anemia but suppresses erythropoiesis of cells containing Hb S in the patient's bone marrow and leaves him or her with a majority of cells containing Hb A. This provides a safety net in case a sickle-inducing insult occurs despite the best efforts to avoid one. Individuals with sickle hemoglobinopathies may require any of the operations common to all children, for example, herniorrhaphy, appendectomy, tonsillectomy, and circumcision, but a significant number will develop calcium bilirubinate cholelithiasis and possibly cholecystitis as a result of the continual increased load of bile salts resulting from the shortened lifespan of the cells containing Hb S. Also, although most individuals with Hb S will gradually suffer splenic infarction by late childhood, a significant number of infants will experience acute splenic sequestration crisis, a life-threatening entity, the recurrence of which is prevented by splenectomy. Several publications have demonstrated that such surgical procedures can be performed in large numbers of patients with sickle hemoglobinopathies without deaths and with minimal morbidity.

Adolescent↗
PubMed1992

The technique of laparoscopic cholecystectomy in children.

Twelve children underwent elective laparoscopic cholecystectomy for symptomatic cholelithiasis during a 10-month period in one institution. The operative technique that has been described for adults was modified because of the smaller dimensions of pediatric patients. These modifications are discussed in this report, as are new alternatives for evaluating the common duct. No operative complications or conversions to open cholecystectomy occurred, and no complications after surgery were seen during an average follow-up period of 4.5 months. The benefits of laparoscopic cholecystectomy include decreased pain and ileus after surgery, shortened hospitalization, and improved cosmesis. Laparoscopic cholecystectomy is safe and efficacious in children, and it compares favorably with traditional cholecystectomy in the pediatric age group.

Adolescent↗
PubMed1991

Induction of T cell CD7 gene transcription by nonmitogenic ionomycin-induced transmembrane calcium flux.

The CD7 molecule is a 40-kDa member of the Ig superfamily that has structural homology to the murine Thy-1 molecule and is acquired early in human T cell ontogeny. Previous studies have demonstrated that expression of the CD7 molecule is markedly up-regulated during T cell activation. In this study, we have studied the signals required for CD7 up-regulation on human T cells. We found that nonmitogenic amounts of ionomycin selectively and maximally up-regulated T cell CD7 on mature (peripheral blood) T cells after 24 h. Whereas CD7 expression was increased 78 +/- 25% by 0.5 microM ionomycin, expression of CD25 (IL-2R alpha), class II MHC, 4F2, transferrin receptor, CD2, CD3, CD4, CD5, and CD8 molecules was not increased. Ionomycin-induced CD7 surface expression was associated with peak increases in CD7 mRNA after 4 to 6 h. Transcriptional analysis and CD7 mRNA half-life determination revealed the increase in CD7 mRNA was the result of increased CD7 gene transcription 1 h after ionomycin stimulation and was not due to prolongation of CD7 mRNA half-life. The up-regulation of surface CD7 expression by ionomycin was dependent on extracellular calcium and did not require the activation of T cell tyrosine protein kinase. Mitogenic CD2 and CD3 mAb as well as stimulation of T cells by PHA also up-regulated CD7 expression. CD7 up-regulation by ionomycin was transient (24 to 72 h) and inhibitable by cyclosporin A, whereas CD7 up-regulation by PHA was sustained over 5 to 7 days and was significantly less inhibitable by cyclosporin A. These data demonstrate that induction of a transmembrane calcium flux generates signals that lead to CD7 gene transcription.

Antibodies, Monoclonal↗
PubMed1991

Paroxysmal nocturnal hemoglobinuria with onset in childhood and adolescence.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic disorder characterized by hemoglobinuria, thrombosis, infection, and a tendency toward bone marrow aplasia. Onset usually occurs in adulthood. Few children and adolescents with PNH have been described, and data on diagnosis, clinical course, and survival in young patients are unavailable. METHODS: We retrospectively reviewed clinical and laboratory data on all patients 21 years old or younger in whom PNH had been diagnosed at Duke University Medical Center from 1966 to 1991. RESULTS: Medical records and clinical follow-up data were available for 26 young patients. Although 50 percent of adult patients present with hemoglobinuria, only four of our patients (15 percent) presented with this feature. In contrast, 15 of our patients (58 percent) had moderate or severe bone marrow failure at presentation, as compared with about 25 percent of adults in cases from the literature; all 26 patients eventually had evidence of bone marrow dysfunction. Eight patients (31 percent) have died, with a median survival of 13.5 years since their initial symptoms. CONCLUSIONS: Children and adolescents with PNH have a greater prevalence of bone marrow failure than do adults with this disorder, and their morbidity and mortality are high. Bone marrow transplantation should be considered for selected young patients with PNH.

Adolescent↗
PubMed1991

Transient erythroblastopenia in the first year of life.

The distinction between transient erythroblastopenia of childhood (TEC) and congenital red cell aplasia (Blackfan-Diamond anemia) is usually possible at presentation using clinical and laboratory data. When hypoplastic anemia occurs in the first year of life, however, the distinction is more difficult. We describe 7 infants with hypoplastic anemia who illustrate this diagnostic dilemma.

Anemia, Aplastic↗
PubMed1991

Analysis of clones derived from human CD7+CD4-CD8-CD3- thymocytes.

The differentiation of human thymocyte precursors was studied by analysis of clonal progeny of CD4-CD8-CD3- (triple negative or TN) thymocytes. Using a culture system of phytohemagglutinin, IL-2, and irradiated allogeneic lymphoid feeder cells, we found that 48% of clones (104 total) derived from TN thymocyte suspensions were TCR gamma delta cells, 12% of clones were TCR alpha beta cells, and 34% were CD16+CD3- cells. Importantly, 6% of clones were novel subsets of CD4+CD8-CD3- or CD4-CD8+CD3- thymocytes. The majority of TCR alpha beta, TCR gamma delta, and CD16+CD3- clones expressed low levels of CD4. Molecular analysis of freshly isolated TN- thymocytes prior to in vitro culture demonstrated that up to 40% of cells had TCR gamma, delta, and beta gene rearrangements, but were negative in indirect immunofluorescence assays for cytoplasmic TCR delta and beta. These data provide evidence at the clonal level for the presence of precursors of the TCR alpha beta and TCR gamma delta lineages in the human TN thymocyte pool. Moreover, a substantial proportion of freshly isolated human TN thymocytes had already undergone TCR gene rearrangement prior to in vitro culture. Whether these precursors of the TCR alpha beta and TCR gamma delta lineages mature from cells already containing TCR gene rearrangements into sTCR+ cells or differentiate in vitro from cells with TCR genes in germline configuration remains to be determined. Nonetheless, these data demonstrate that the predominant clone types that grow out of human TN thymocytes in vitro are TCR gamma delta and NK cells.

Antigens, CD↗
PubMed1990

Long-term management of splenic sequestration in children with sickle cell disease.

We describe our experience with 23 children with sickle cell disease and splenic sequestration crisis, emphasizing our management approaches and the patients' subsequent clinical courses. Our data illustrate that sequestration crisis may occur despite a reduction in hemoglobin S concentration to less than 30% of the total hemoglobin mass. In addition, the risk of recurrent splenic sequestration was similar for patients who received transfusion therapy and for those who were simply observed. We conclude that a short-term transfusion program to prevent recurrent splenic sequestration is of limited benefit.

Anemia, Sickle Cell↗
PubMed1989

Characterization of the surface topography and putative tertiary structure of the human CD7 molecule.

The CD7 gp40 molecule is a member of the Ig gene superfamily and is expressed on T cell precursors before their entry into the thymus during fetal development. N-terminal amino acids 1-107 of CD7 are highly homologous to Ig kappa-L chains whereas the carboxyl-terminal region of the extracellular domain of CD7 is proline-rich and has been postulated to form a stalk from which the Ig domain projects. To define potential functional regions of CD7, we have studied the surface topography of the CD7 Ag by synthesizing peptides corresponding to linear sequences within the CD7 extracellular domains, by raising polyclonal anti-CD7 rabbit sera against these peptides, and by computer analysis of the primary CD7 amino acid sequence. Polyclonal anti-CD7 sera were studied using indirect immunofluorescence, RIA, radioimmunoprecipitation, and Western blot assays. Computer analysis was performed comparing the CD7 sequence with all other known protein sequences. We found that three CD7 epitopes defined by peptides CD7-1A (AA 1-38), CD7-4 (AA 48-74), and CD7-7 (AA 129-146) were available for binding antibody on the surface of the CD7 molecule. Using computer analysis, we transposed the amino acid sequence of the CD7 Ig kappa-like N-terminal domain of CD7 onto the spatial coordinates of REI, a previously reported Ig kappa-molecule highly homologous (48%) to the CD7 N-terminal Ig-like region. Based on computer analysis of this putative CD7 three-dimensional structure, both the CD7-1A and CD7-4 regions protruded from the surface of the N-terminal domain of the CD7 molecule. Finally, comparison of the CD7 transmembrane sequence with CD4 and HIV transmembrane sequences and with respiratory syncytial virus fusion sequences demonstrated similar sequence motifs among these molecules.

Amino Acid Sequence↗
PubMed1976

An operation for relief of severe left ventricular outflow tract obstruction.

The case history of a 30-year-old man with severe mitral and aortic stenosis and slight aortic regurgitation who underwent replacement of both valves is presented. At the initial surgical procedure, because of the small-size annuli, a small Beall mitral prosthesis and a No. 19 Björk-Shiley aortic prosthesis were used. The subsequent recurrence of severe symptoms and findings of an 80 mm. Hg gradient across the Björk-Shiley aortic valve led to repeat exploration and corrective surgery. The operative procedure to relieve left ventricular outflow obstruction is described. It is felt that this procedure can be used not only for the relief of severe aortic annular stenosis but also for other forms of severe left ventricular outflow tract obstruction such as idiopathic hypertrophic subaortic stenosis and particularly in the patients who have experienced poor results with one of the known surgical procedures for this clinical entity.

Adult↗