Search PubMed⌕ Search

Biomedical subjects

A Perez

Publications and source records attributed to A Perez.

At least 127 records · Page 7Linked to original sources
PubMed1993

Characterization of lineage-negative blast subpopulations derived from normal and chronic myelogenous leukemia bone marrows and determination of their responsiveness to human c-kit ligand.

Lineage-negative (lin-) normal and chronic myelogenous leukemia (CML) marrow blast populations were obtained by negative selection and subsequently separated on the basis of size by velocity sedimentation. The three subpopulations of lin- blasts obtained were enriched for F8 (the more primitive small blasts), F11 (blasts intermediate in size), and F13 (the more mature large blasts). We examined the morphological and phenotypic characteristics and cell cycle status of the subpopulations and determined the responsiveness of granulocyte-monocyte progenitors (colony-forming units/granulocyte-macrophage) derived from each subpopulation to mast cell growth factor in combination with granulocyte (G-CSF) or granulocyte-macrophage (GM-CSF) colony-stimulating factors alone and in combination. Morphological assessment revealed that an increased proportion of CML lin- blasts exhibited early cytoplasmic maturation as evidenced by the appearance of azurophilic (nonspecific) granules in the cytoplasm. Although the percentages of CML and normal small blasts expressing CD34 were similar, the proportion of CML lin- blasts expressing CD34 declined in the intermediate and more mature large lin- blast subpopulations by about 50%, whereas the percentage of CD34+ normal blasts remained essentially the same, indicating an earlier loss of CD34 expression by CML lin- blasts. In addition, the percentages of CML small blasts expressing CD33 were higher than normal (26-61% versus 0-16%, respectively), indicating that a higher proportion of CML small lin- blasts had a more mature phenotype. Mast cell growth factor addition to cultures stimulated by G-CSF, GM-CSF, or G-CSF plus GM-CSF, exerted the greatest synergistic effect (increased colony number and size) in the normal small and intermediate lin- blast cultures, but mast cell growth factor had considerably less effect, or no effect, in cultures of comparable CML subpopulations, indicating that CML lin- progenitors had a somewhat lower requirement for multiple growth factors. The findings suggest that the differences observed between normal and CML marrow subpopulations are proportional differences and that a greater proportion of CML lin- blast subpopulations exhibit characteristics associated with a more advanced stage of maturation than comparable normal lin- blast subpopulations.

Bone Marrow↗
PubMed1993

PMLRAR homodimers: distinct DNA binding properties and heteromeric interactions with RXR.

Fusion proteins (named PMLRAR) between PML and the retinoic acid receptor alpha (RAR alpha) are generated as a result of the t(15;17) chromosomal translocation found in acute promyelocytic leukemia (APL). We show here that PMLRAR proteins exist in solution as stable homodimers whose formation is mediated by a presumptive coiled coil in the PML moiety. In contrast to RAR alpha, which requires heterodimerization with RXR for efficient DNA binding, PMLRAR homodimers can bind to target sequences in the absence of RXR, and the binding pattern of PMLRAR homodimeric complexes to directly repeated motif (DR) response elements with 1-5 bp spacers is different from that of RAR/RXR heterodimeric complexes. We show that the presence of RXR induces the formation of PMLRAR/RXR heteromeric complexes which bind to DNA via one RAR DNA binding domain (DBD) and one RXR DBD, like 'classical' RAR/RXR heterodimers. PMLRAR interaction with RXR occurs in solution and in transfected cultured Cos cells, and PMLRAR is able to sequester RXR efficiently in the cytoplasm, suggesting that dominant 'inactivation' of RXR may be a possible mechanism of action for PMLRAR. Accordingly, we show that PMLRAR can both prevent the binding of the vitamin D3 receptor (VDR) to a target sequence in vitro and inhibit vitamin D3-dependent activation of a VDR-responsive reporter gene in transfected cells. These results suggest that both the distinct DNA binding properties of PMLRAR homodimers and the sequestration of RXR by PMLRARs may contribute to the molecular mechanisms which underlie the pathogenesis of APL. We also report that RXR alpha transcripts are down-regulated by RA-treatment in promyelocytic cells.

Amino Acid Sequence↗
PubMed1993

Differences in the composition and in the efficiency of red cell production of normal and CML erythroid progenitor populations are highlighted by response to human c-kit ligand.

Previous studies have suggested that erythroid progenitors derived from patients with chronic myelogenous leukemia (CML) in chronic phase may have reduced proliferative capacity. Considering recent evidence that mast cell growth factor (MGF) enhances the proliferative capacity of normal erythroid burst-forming units (BFU-E), we examined whether MGF could increase the proliferative potential of CML erythroid progenitors to normal capacity. To evaluate the total proliferative capacity achieved, the BFU-E were divided into four subpopulations (XL = extra large, L = large, M = medium, S = small) and colonies were aspirated to determine the cellularity of BFU-E from each subpopulation. MGF alone or in combination with MoT cell line conditioned medium (MoCM) or granulocyte-macrophage colony-stimulating factor (GM-CSF) + interleukin-3 (IL-3) significantly increased the proliferative capacity of erythropoietin (EPO) dependent CML and normal BFU-E. Although the total number of BFU-E generated were similar, the number of BFU-E with high proliferative potential were considerably less in CML BFU-E populations. BFU-E designated XL (129,000-431,000 cells) were only found in MGF cultures and only normal BFU-E had this proliferative capacity. BFU-E designated L were increased in both normal and CML BFU-E populations but less CML BFU-E had this proliferative capacity (mean number 25% of normal) and CML L BFU-E from 2/3 CML patients comprised fewer cells than normal L BFU-E. Normal BFU-E populations comprised 16-24% high proliferative BFU-E (XL + L) in contrast to 4-5% high proliferative BFU-E (L only) comprising CML BFU-E populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1993

High fiber diets slow bone turnover in young men but have no effect on efficiency of intestinal calcium absorption.

Dietary fiber reduces the absorption of dietary calcium from a meal, but its impact on calcium kinetics is unknown. We therefore evaluated the effects of a high fiber diet on calcium balance and kinetics and on calcium-regulating hormones. Seven young men each participated in two 23-d experiments. In the low fiber period the controlled diet provided 6.5 g fiber/d and 530 mg calcium/d. In the high fiber period fiber was increased to 31.3 g/d and calcium to 586 mg/d by substituting high fiber cereal. Measured between d 7 and 12 of each period, the high fiber diet significantly lowered the apparent absorption of calcium (from 60.6 +/- 23.8% to 37.1 +/- 26.5%) and reduced calcium balance, although balance remained positive overall. Fiber had no effect on serum total or ultrafiltrable calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D or parathyroid hormone concentrations measured on d 1, 7, 12 and 20. Calcium kinetics was studied between d 17 and 23 by administering oral 44Ca and intravenous 42Ca to fasting subjects. Fractional absorption of calcium in the fasting state was unaffected by fiber. However, during the high fiber period, subjects had significantly lower bone accretion, resorption and turnover rates, and calcium flow to bone from the exchangeable pool than during the low fiber period. We conclude that the fiber-induced reduction in calcium absorption slowed down bone calcium turnover but did not increase the efficiency of intestinal absorption.

Adult↗
PubMed1993

Erythema elevatum diutinum associated with celiac disease: response to a gluten-free diet.

An 11-year-old girl with a history of insulin-dependent diabetes mellitus had erythema elevatum diutinum (EED) associated with a celiac disease related to a possible kidney disease. Dapsone did not improve the skin manifestations. However, the lesions disappeared after a gluten-free diet was begun. To our knowledge, this report describes the first case of EED in a patient with celiac disease.

Celiac Disease↗
PubMed1993

Neurologic complications in liver transplantation.

A retrospective review is presented of neurologic complications in our first 143 consecutive adult patients (208 liver transplants in 143 adults and 18 children) undergoing liver transplantation. Nineteen (13.2%) of the 143 patients developed neurologic complications in the postoperative period. Immunosuppression was initiated intraoperatively with steroids with the addition of azathioprine on Day 1 and cyclosporine, adjusted by RIA to a level of 400-600 ng/ml, on Day 2 post-transplantation. Azathioprine is discontinued in the third month. Fourteen of the 19 patients (73.6%) presented with CNS complications characterized by: diffuse multifactorial encephalopathy (5 patients); leukoencephalopathy (2 patients) which required temporary (1 case) or permanent (1 case) discontinuation of cyclosporine A; hemorrhage (in 2 cases due to arterial hypertension and coagulopathy and another due to unknown causes); ischemic/anoxic injury secondary to cardiorespiratory arrest (2 patients) or arteriothrombosis (1 patient); and myelopathy (1 patient) due to vertebral compression (T10-T11) secondary to osteoporosis. The diagnostic studies most often employed were computed tomographic (CT) (85.7%) and electroencephalography (EEG) (42.8%). Five of 19 patients (26.3%) suffered peripheral nervous system (PNS) complications: 1 patient with reversible Claude-Bernard-Horner Syndrome caused by central venous catheterization during anesthesia; 2 patients with peroneal nerve palsy due to compression below the knees by operating room table supports; 1 patient with an irreversible lesion of the right recurrent laryngeal nerve secondary to prolonged intubation and central venous catheterization; and 1 patient with a reversible lesion of the left brachial plexus secondary to inadvertant hyperextension of the upper extremity on the O.R. table due to the need for dialysis and catheterization of the axillary vein for veno-venous bypass.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Integration of molecular and biological abnormalities in quest for selective treatment of chronic myelogenous leukemia (CML).

CML is an excellent target for development of selective treatment because of its highly consistent genetic abnormality t(9;22) and unique fusion gene product, p210bcr/abl, although it is not yet clear what form of specific therapy might be effective. Several components of p210bcr/abl are thought to be essential for its transforming activity: These include the constitutive tyrosine kinase activity of abl and the ability of the first exon for bcr both to specifically bind to abl's SH2 binding domain and possibly also to function as a novel type of serine kinase. Relatively little is yet known about what specific abnormalities in the regulatory pathways are caused by the altered tyrosine kinase activity of p210bcr/abl and other bcr/abl oncoproteins, but whatever its precise mode of action proves to be, p210bcr/abl presumably somehow changes the normal pattern of phosphorylation of key regulatory proteins in the signaling pathways so that the genes which normally direct the orderly sequence of proliferation and maturation of the myeloid progenitors are not properly regulated. The end results of this 'disregulation' are that there is asynchronous or discordant maturation; relative to comparable normal progenitors, a higher proportion of CML progenitors exhibit earlier cytoplasmic and delayed nuclear maturation. The leukemic progenitors do not proliferate more rapidly than comparable normal progenitors or have increased ultimate proliferative potential, but they go through one or more additional divisions during passage through the later maturation compartments and also live longer, resulting in overexpansion of the leukemic population. It is important to recognize the close linkage between maturation and proliferation in designing experiments to correlate the molecular and biological abnormalities and in seeking novel therapies to selectively affect the leukemic progenitors.

Bone Marrow↗
PubMed1993

[Acute gastric volvulus in a patient with asplenic syndrome].

A 18 month-old boy with asplenic syndrome was admitted to our hospital with a twelve hours history of mucous vomiting, abdominal pain and a round epigastric mass. It was diagnosed as having a gastric volvulus and an emergency laparotomy was performed. The stomach was situated at the right side and a mesenterioaxial volvulus was found, with cyanosis of the antrum. The gastrophrenic and gastrosplenic ligaments were absent. The clinical and radiological characteristics of asplenic syndrome are reviewed. The pediatric surgeons must be aware of the digestive malformations of the asplenic syndrome, because some of that like malfixation of the stomach could be the cause of an acute abdomen.

Acute Disease↗
PubMed1993

Biological monitoring of workers at a recently opened hazardous waste disposal site.

A health assessment was performed in a recently opened landfill for toxic waste. The site has received 14,000 tons of hazardous waste, confined in drums or deposited as bulk material, which were left outdoors for seven months. The analysis in some samples showed that the waste is rich in heavy metals, however we did not find high levels of contaminates in air or surface soil in different areas on-site. When compared to a control group, high-risk workers show higher levels of arsenic in urine and hair, and non-specific symptoms (irritability and insomnia). But among groups, we did not find statistical differences in urinary mercury, blood lead, phenol in urine, cadmium in hair or blood, sister chromatid exchange values, lymphocytes proliferation kinetics, liver function tests, and other non-specific symptoms. We considered this project as a background study for human exposure to hazardous waste, providing useful results for the future evaluation of chronic effects in the same population.

Adult↗
PubMed1992

Constitutive expression of p53 protein in enriched normal human marrow blast cell populations.

Previous studies by others using metabolic labeling, cell lysis, and immunoprecipitation have reported elevated levels of p53 protein in blast cells derived from patients with acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML), whereas p53 protein was not detected in normal light-density bone marrow cells. In this report, using the same detection methods, we confirm the negligible expression of p53 protein in normal light density marrow cells. However, we find clearly significant levels of p53 protein expression in enriched normal human marrow blast populations. Furthermore, using a panel of p53 specific monoclonal antibodies, we find the p53 protein constitutively synthesized by normal marrow blasts has the immunologic phenotype identified by PAb240 that reportedly recognizes a common conformational-dependent epitope on mutant p53. We have also found that the p53 immunologic subclass identified by PAb240 exists in normal human circulating lymphocytes either resting, serum starved, or PHA activated. In summary, it is clear that (1) normal marrow blast populations provide the appropriate control for assessing the levels of p53 protein expression in leukemic blast cells; and (2) PAb240 cannot be used to distinguish p53 mutated at the DNA level from normal p53 in fresh human hematopoietic cells.

Antibodies, Monoclonal↗
PubMed1992

Structure, localization and transcriptional properties of two classes of retinoic acid receptor alpha fusion proteins in acute promyelocytic leukemia (APL): structural similarities with a new family of oncoproteins.

Acute promyelocytic leukemia (APL) is due to a chromosomal t(15;17) translocation which involves a novel human gene, Myl, (also named PML) and the retinoic acid (RA) receptor alpha (RAR-alpha) gene. We report here the characterization of Myl and of the reciprocal MylRAR (PMLRAR) and RARMyl (RARPML) fusion transcripts which are found in two classes of APL patients. Myl displays similarities with a new family of proteins of which some members are fused to protooncogenes in the transforming proteins RFP-ret and T18. The speckled nuclear localization of Myl, as well as its sequence homology with the 52 kDa component of the RO/SSA ribonucleoprotein particle, suggest that Myl may be present in a ribonucleoprotein complex. In contrast to both Myl and RAR-alpha whose localization is essentially nuclear in the presence or absence of RA, MylRAR which is largely cytoplasmic in the absence of RA appears to be translocated to the nucleus in the presence of RA. Myl and MylRAR can associate in vitro and this association is mediated by a coiled coil in the Myl sequence. In vivo this association results in a colocalization of Myl and MylRAR which is identical to that of MylRAR alone. Studies of activation of transcription from the promoters of several RA target genes indicate that MylRARs have altered transcription activation properties when compared with RAR-alpha. Most notably, MylRAR represses markedly the activity of some RA target promoters in the absence of RA. Western blot analyses of patient samples show that MylRAR is expressed to a much higher level than wild type RAR-alpha originating from the normal allele. Taken together, these results suggest that MylRAR may interfere in a dominant manner with both Myl and RAR functions.

Alleles↗
PubMed1991

The effects of transforming growth factor beta 3 on the growth of highly enriched hematopoietic progenitor cells derived from normal human bone marrow and peripheral blood.

The effects of transforming growth factor beta 3 (TGF-beta 3) on growth in semisolid cultures of enriched hematopoietic progenitors derived from normal human marrow and blood were evaluated. Conditioned media from the Mo-T cell line (MoCM) were the source of colony-stimulating factors used to optimally stimulate primitive progenitors. To assess whether a proportion of granulocyte/monocyte (GM) progenitors were prevented from cycling, all sizes of GM aggregates were evaluated from 3 to 20 days. The activity of TGF-beta 3 on the growth of erythroid burst-forming units (BFU-E) and granulocyte-macrophage colony-forming units (CFU-GM) was similar to that observed for TGF-beta 1. TGF-beta 3 (10, 100, and 1,000 pmol/liter), added initially or 72 h after initiation of culture, did not significantly affect the total number of marrow GM aggregates at 3, 7, 14, and 20 days, but TGF-beta 3 (1,000 pmol/liter), added initially, reduced the total number of blood GM aggregates. This suggests that some blood GM progenitors might be blocked from cycling but that the great majority of marrow GM progenitors are not blocked. Whether TGF-beta 3 (10, 100, and 1,000 pmol/liter) was added initially or after 72 h of stimulation by MoCM, there was a dose-dependent reduction of marrow and blood GM colony size even when the total number of colonies was unaffected. TGF-beta 3 (10, 100, and 1,000 pmol/liter), added initially or at 72 h, reduced in a dose-dependent manner the size of marrow and blood-derived BFU-E. TGF-beta 3 (1,000 pmol/liter) was more likely to reduce the total number of marrow and blood BFU-E, and this increased sensitivity of the erythroid lineage may prevent the development of this population in colonies derived from multipotential colony-forming unit-granulocyte/erythroid/monocyte (CFU-GEM). The results suggest that the main effect of TGF-beta 3 and TGF-beta 1 is to slow the rate of proliferation of hematopoietic progenitors rather than to prevent them from beginning proliferation. This results in a reduction in colony size which prevents the identification of primitive versus mature progenitor on the basis of standard criteria of colony size.

Bone Marrow↗
PubMed1991

Efficacy studies in natural family planning: issues and management implications illustrated with data from five studies.

Studies of method effectiveness must be carefully assessed for comparability of findings. Several parameters are identified that are important in the assurance of comparable results. This article discusses these issues with the use of data from previously published studies and emphasizes the management implications of use-effectiveness data.

Data Interpretation, Statistical↗