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Biomedical subjects

L Cripe

Publications and source records attributed to L Cripe.

8 recordsLinked to original sources

Low expression of the myeloid differentiation antigen CD65s, a feature of poorly differentiated AML in older adults: study of 711 patients enrolled in ECOG trials.

CD65s appears when the progenitor antigen CD34 disappears, suggesting that this sialylated carbohydrate antigen marks a turning point in normal myeloid differentiation. We characterized acute myeloid leukemia (AML) with low CD65s expression (CD65s(low) AML) in 711 patients entered on seven Eastern Cooperative Oncology Group AML treatment trials (1986-1999). Of those, 198 (28%) qualified as having CD65s(low) AML. Morphologically, CD65s(low) AML was more common in FAB subgroups with minimal differentiation, M0/M1 (P=<0.0001). Early precursor antigens CD34, CD117 and terminal transferase were more frequent in CD65s(low) than CD65s(high) AML (P=<0.0001). Myeloperoxidase was present in fewer CD65s(low) myeloblasts, and the more mature myeloid antigens, CD15 and CD11b, were rarely detected (P=<0.0001). Yet, the two diagnoses did not differ in the distribution of cytogenetic prognostic groups or the occurrence of the multidrug-resistance mediator, P-glycoprotein. CD65s(low) AML patients were significantly older than CD65s(high) cases (P<0.0001). Furthermore, the incidence of CD65s(low) cases increased with age, from 20% in patients under the age of 50 years to 67% in patients older than 80 years (P<0.0001). Overall, complete remission (CR) rate and overall survival were comparable in CD65s(low) and CD65s(high) AML. However, among patients >55 years of age, CD65s(low) AML had a decreased CR rate of 33 vs 44% in CD65s(high) AML (P=0.055). Thus, CD65s(low) AML represents immunophenotypically undifferentiated disease and occurs predominantly in older adults. Although not statistically significant, the observed association between low CD65s expression and decreased CR rate only in patients over the age of 55 is intriguing.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The exodus subfamily of CC chemokines inhibits the proliferation of chronic myelogenous leukemia progenitors.

Chemokines are a family of related proteins that regulate leukocyte infiltration into inflamed tissue and play important roles in disease processes. Among the biologic activities of chemokines is inhibition of proliferation of normal hematopoietic progenitors. However, chemokines that inhibit normal progenitors rarely inhibit proliferation of hematopoietic progenitors from patients with chronic myelogenous leukemia (CML). We and others recently cloned a subfamily of CC chemokines that share similar amino-terminal peptide sequences and a remarkable ability to chemoattract T cells. These chemokines, Exodus-1/LARC/MIP-3alpha, Exodus-2/SLC/6Ckine/TCA4, and Exodus-3/CKbeta11/MIP-3beta, were found to inhibit proliferation of normal human marrow progenitors. The study described here found that these chemokines also inhibited the proliferation of progenitors in every sample of marrow from patients with CML that was tested. This demonstration of consistent inhibition of CML progenitor proliferation makes the 3 Exodus chemokines unique among chemokines. (Blood. 2000;95:1506-1508)

Cell Division↗

Assessment of fetal rhythm in complete congenital heart block by magnetocardiography.

We report high precision assessment of fetal rhythm in utero in a case of isolated congenital complete heart block using fetal magnetocardiography. The recordings reveal a remarkably strong tendency for the atria and ventricles to synchronize, which is manifested by the continual presence of ventriculophasic sinus arrhythmia and frequent episodes of accrochage and isorhythmic AV dissociation.

Adult↗

Ventricular noncompaction and distal chromosome 5q deletion.

We describe a 7 1/2-year-old girl with mildly unusual phenotype and complex heart disease including ventricular myocardial noncompaction. She was found to have a distal 5q deletion, del(5)(q35.1q35.3). Fluorescent in situ hybridization showed that this deletion included the locus for the cardiac specific homeobox gene, CSX. This suggests that some instances of ventricular myocardial noncompaction may be caused by haploinsufficiency of CSX.

Child↗

Autologous transplantation of mobilized peripheral blood CD34+ cells selected by immunomagnetic procedures in patients with multiple myeloma.

In the use of autologous PBPC transplantation in patients with multiple myeloma, contamination of PBPC with myeloma cells is commonly observed. Enrichment for CD34+ cells has been employed as a method of reducing this contamination. In this study the reduction of myeloma cells in PBPC was accomplished by the positive selection of CD34+ cells using immunomagnetic bead separation (Isolex 300 system). PBPC were mobilized from 18 patients using cyclophosphamide (4.5 g/m2) and G-CSF (10 microg/kg/day). A median of two leukaphereses and one selection was performed per patient. The median number of mononuclear cells processed was 3.50 x 10(10) with a recovery of 1.11 x 10(8) cells after selection. The median recovery of CD34+ cells was 48% (range 17-78) and purity was 90% (29-99). The median log depletion of CD19+ cells was 3.0. IgH rearrangement, assessed by PCR, was undetectable in 13 of 24 evaluable CD34+ enriched products. Patients received 200 mg/m2 of melphalan followed by the infusion of a median of 2.91 x 10(6)/kg CD34+ cells (1.00-16.30). The median time to absolute neutrophil count >0.5 x 10(9)/l was 11 days, and sustained platelet recovery of >20 x 10(9)/l was 14 days. We conclude that immunomagnetic-based enrichment of CD34+ cells results in a marked reduction in myeloma cells without affecting engraftment kinetics.

Adult↗

Perinatal transmission and maternal risks of human papillomavirus infection.

We conducted a prospective study to investigate whether human papillomavirus (HPV) could be vertically transmitted to neonates. Pregnant women (N = 203) were tested for HPV DNA infection during the third trimester and again during labor prior to delivery. Their newborns (N = 203) were tested 1 to 3 days after delivery. Among the mothers, 12.3% (N = 25/203) typed HPV positive at either or both maternal specimen collection periods, whereas only 1.0% of the neonates (N = 2/203) typed positive. This low transmission rate may be due in part to the fact that 65% of mothers who were HPV positive during the third trimester tested HPV negative by labor/delivery. The higher frequency of risks associated with maternal HPV infection were similar to those found in studies of cervical dysplasia and cancer: younger age at first intercourse and first pregnancy, number of sexual partners, and longer duration in use of oral contraceptives. In addition, those who were past smokers and had a shorter recency and latency period in smoking were more likely to be detected with HPV.

Adolescent↗

Vimentin mRNA location changes during muscle development.

The mRNAs for some cytoskeletal proteins are localized, suggesting that mRNA for these proteins may concentrate at sites appropriate for assembly. To test this hypothesis, we observed vimentin mRNA in developing chicken muscle cultures by in situ hybridization with a digoxigenin-labeled DNA probe to vimentin, detected by confocal microscopy using fluorescent anti-digoxigenin antibody. This method has submicrometer resolution. In developing muscle, vimentin mRNA was bipolar in young myoblasts, somewhat perinuclear in elongated myoblasts and spread fibroblasts, and diffuse in young and developing myotubes. In mature myotubes, vimentin mRNA occurred at costameres with vimentin protein. Localization of mRNA may prove important for assembling and maintaining differentiated cytoskeletal structures, as it is for organizing the embryo.

Animals↗