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Biomedical subjects

A Perez

Publications and source records attributed to A Perez.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Relationship of transfusion and infectious complications after gastric carcinoma operations.

To determine the effect of transfusion on the incidence of postoperative infection, a retrospective cohort study of 196 patients who underwent surgery for gastric carcinoma in the period from 1985 through 1989 was carried out. Seventy-one patients (36.2%) developed postoperative septic complications; they had received an average of 4.2 blood units, as compared with 2.7 units received by patients not affected (p less than 0.0053). The hypothesis of dose-response relationship is supported by the Mantel-Haenszel test, as applied to the overall results (p less than 0.01) and the results grouped by duration of operation (p less than 0.02). Furthermore, logistic regression analysis shows transfusion to be an independent risk factor in the incidence of infection (p less than 0.01), as are antibiotic prophylaxis (p less than 0.015), urinary tract catheterization (p less than 0.002), and the duration of surgery (p less than 0.027). This significance is attained after adjustment for age, gender, period of evolution of symptoms; preoperative infection(s), number of white cells, hemoglobin level and total proteins on diagnosis, location of tumor, tumor, nodes, and metastasis staging, operative technique, drainage of the area of operation, enteral nutrition, and the histologic studies and macroscopic appearance of the tumor. This study is further evidence that transfusion may cause an increased incidence of postoperative infection.

Aged↗
PubMed1991

Post-partum cervical mucus: biological and rheological properties.

In this study we have evaluated the score, sperm migration and ultrastructural characteristics of cervical mucus present in amenorrhoeic women under exclusive breastfeeding at 30, 60, 90, 120, 150 and 180 days post-partum. Periovulatory mucus samples from seven normally cycling women were used as a control. The average scores of post-partum and periovulatory mucus were 4.6 +/- 0.4 and 14.1 +/- 0.5 respectively. Twenty-one (39%) of the 54 post-partum cervical mucus samples and all (100%) periovulatory mucus samples allowed sperm migration. Positive sperm migration into post-partum mucus was observed at all time intervals studied. The only parameter that correlated with sperm migration into post-partum mucus was ferning formation. Sperm migration was obtained in all post-partum mucus samples with a score greater than 8, but samples with scores between 2 and 7 also showed sperm penetration. Scanning electron microscopic studies showed the characteristic spongy appearance of periovulatory mucus. Post-partum mucus was formed by a dense mesh (rocky appearance), when samples were generally unable to sustain sperm migration, but samples where sperm migration occurred showed small areas of spongy mucus mixed with areas in which a dense mesh and high cellularity was observed.

Amenorrhea↗
PubMed1991

Effect of L-asparaginase on insulin secretion from isolated rat islets of Langerhans.

The effects of L-asparaginase were evaluated on glucose-induced insulin release from isolated rat islets of Langerhans. Islets were obtained by enzymatic digestion of pancreas from Sprague-Dawley rats. The study of L-asparaginase effects on insulin secretion was performed in a static incubation of islets. Insulin secretion was measured at 60 min of incubation with different secretagogues with and without L-asparaginase. L-Asparaginase at concentrations from 310 to 5,000 U/ml could inhibit the glucose-induced insulin secretion in a dose-dependent manner. This effect was not recovered after incubation in the absence of the drug for another 2 h. The half-maximal inhibitory effect of the enzyme on insulin secretion was observed at L-asparaginase concentrations of 1,000 U/ml. Tolbutamide (200 microM) and ketoisocaproic acid (20 mM) did not induce insulin secretion in the presence of moderately high L-asparaginase concentrations. L-Asparaginase did not inhibit glucose-induced insulin secretion in the presence of isobutyl-methyl-xanthine (IBMX) (20 microM) or forskolin (20 microM). L-Asparaginase promoted a decrease in total c-AMP in isolated rat islets at concentrations from 500 to 1,500 U/ml when they were stimulated by glucose. If islets were treated with IBMX or forskolin, L-asparaginase did not inhibit the glucose-induced total c-AMP levels in islets.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Assessment of attention deficit disorder using a thematic apperception technique.

Attention deficit-hyperactivity disorder (AD-HD) is regarded as being relatively common among school-age children, but the literature reveals a number of confounding factors with standard assessment techniques of the disorder. Using a structured thematic apperception technique (the Tell-Me-A-Story [TEMAS] test) to measure attention to pictorial stimuli depicting characters, events, settings, and covert psychological conflicts, a study was conducted with 152 normal and 95 clinical Hispanic, Black, and White school-age children. Results reveal that the AD-HD children are significantly more likely than normal children to omit information in the stimuli about characters, events, settings, and psychological conflicts. Differences between the groups are large and persistent in the presence of structured inquiries by the test examiners. Results suggest the potential utility of structured thematic apperception techniques for the assessment of AD-HD, eventually to facilitate DSM-III-R (American Psychiatric Association, 1987) diagnosis, but also to invite closer scrutiny in carefully controlled validity studies.

Adolescent↗
PubMed1991

[Fusion proteins between PML and alpha-RAR in acute promyelocytic leukemia].

Acute promyelotic leukemia is characterized by a t(15;17) chromosomal translocation which results in fusion products between PML (chromosome 15) and RAR-alpha (chromosome 17). We describe 2 classes of patients which possess different PMLRAR and RARPML fusion transcripts. We then discuss the functional properties of PML and show that PMLRAR can interfere with both PML and RAR-alpha functions.

Humans↗
PubMed1991

Proliferative response of human acute myeloid leukemia cells and normal marrow enriched progenitor cells to human recombinant growth factors IL-3, GM-CSF and G-CSF alone and in combination.

The effects of human recombinant colony-stimulating factors (r-CSFs), interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) on inducing the growth of colonies derived from patients with acute myeloid leukemia (AML) (CFU-L) were investigated and compared to the proliferative response of CFU-GM derived from highly enriched normal blast cell populations. The effects of GM-CSF and IL-3 alone were similar. Both only minimally stimulated normal colonies derived from CFU-GM when compared to stimulation with MoCM (a mean of 28% of the total colonies and 17% of the colonies greater than 100 cells obtained with MoCM). Similarly, the number of leukemic colonies was substantially less than with MoCM (less than 30% of MoCM) in all but 3/10 AML patients and both were only able to significantly stimulate CFU-L derived colonies greater than 50 cells from 2/10 patients. G-CSF alone stimulated some CFU-L derived colony growth in 9/10 patients but the number stimulated was minimal relative to MoCM in five of the patients and significant stimulation of colonies greater than 50 cells occurred in only one patient. The mean number of normal CFU-GM derived colonies stimulated by G-CSF was 41% of the total colonies and 34% of the colonies greater than 100 cells generated by MoCM. The combination of G-CSF with GM-CSF and G-CSF with IL-3 resulted in a synergistic or additive increase in the number of CFU-L in 5/10 and 7/10 patients, respectively, and a synergistic increase in the size of CFU-L in 5/10. The same combinations resulted in a significant synergistic effect on size of normal CFU-GM derived colonies. There was no evidence of a synergistic increase in the number or size of CFU-L and CFU-GM derived colonies stimulated with GM-CSF in combination with IL-3. In addition, a combination of all three (G-CSF + GM-CSF + IL-3) did not enhance the effect of G-CSF + GM-CSF or G-CSF + IL-3. These results suggest that there is significant heterogeneity among AML patients in the pattern of responsiveness of the leukemic cells to the recombinant growth factors. In addition, their responsiveness does not significantly differ from that of normal progenitors. In view of the current clinical trials with r-CSFs and cytotoxic drugs in AML patients, this issue is important and worthy of further investigation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Prenatal diagnosis of fetal left ventricular aneurysm: a case report and review.

Fetal echocardiography in a 30-year-old black woman, gravida 4, para 3, demonstrated left ventricular aneurysm. This was confirmed by color flow pulsed Doppler techniques. After delivery, neonatal echocardiography and magnetic resonance imaging further confirmed the diagnosis. The infant was followed closely and underwent surgical correction at 8.5 months of age. Before surgery, cardiac catheterization demonstrated normal hemodynamic function. A review of the literature revealed a paucity of information. Issues of prenatal diagnosis, antenatal surveillance, method of delivery, and neonatal follow-up are not well defined in either the obstetric or pediatric cardiology literature. A rationale for our approach to this complex problem is presented.

Adult↗
PubMed1990

Activated T-lymphocytes in newly diagnosed type I diabetic patients: relationship to residual beta cell function.

The relationship between T-lymphocyte activation and residual beta-cell function was studied in 19 newly diagnosed Type I (insulin dependent) diabetic patients, aged 6-43 years, 7-10 days after beginning insulin therapy and once normoglycemia had been achieved. Residual beta-cell function was studied by measurement of plasma C-peptide concentration 6 minutes after intravenous glucagon administration. T-lymphocyte activation markers, HLA-DR/CD3 and interleukin-2 receptor (Tac) expression, were measured in peripheral blood mononuclear cells by dual- or single-colour flow cytometry. Six patients showed increased percentages of activated T lymphocytes (increased HLA-DR positivity in four patients, and an excess of Tac-positive cells in two). The mean percentage of activated T lymphocytes was higher in patients with stimulated C-peptide levels below 300 pmol/l (8.32 +/- 1.32%) than in those with plasma stimulated C-peptide above 300 pmol/l (3.93 +/- 0.49%), P less than 0.01, or controls (3.48 +/- 0.60%), P less than 0.01. Furthermore, the six patients with increased percentages of activated T lymphocytes were in the low stimulated C-peptide group. A negative correlation was found between the percentage of activated T lymphocytes and glucagon-stimulated C-peptide (r = -0.5877, P less than 0.01). We conclude that increased T-lymphocyte activation is associated with a higher impairment of beta-cell function at the onset of Type I diabetes mellitus.

Adolescent↗
PubMed1990

Pharyngeal adenocarcinoma with intestinal features.

A high grade adenocarcinoma arising primarily in the pharynx of a 67-year-old man is presented. A CT-scan revealed a tumour mass growing in the pharynx, largely affecting parapharyngeal soft tissues. Lymph node metastases were found at clinical presentation. Both morphological and immunohistochemical studies displayed similar features to those of intestinal origin. To our knowledge, no previous examples of such neoplasm have been reported at this site. Its possible histogenetical origin is discussed.

Adenocarcinoma↗
PubMed1990

Permeable cell models in stimulus-secretion coupling.

A number of mechanical and chemical methods have been developed to achieve selective permeabilization of the plasma membrane. These methods have been applied to many cell types and have proven to be highly useful for studying stimulus-secretion coupling mechanisms. Thus far, this approach has contributed significantly to our understanding of phosphoinositide metabolism and the regulation of intracellular calcium. The permeabilization techniques also have contributed important information regarding cAMP-dependent pathways. In addition to studies of stimulus-secretion coupling, permeabilized cell preparations can be employed for investigations of enzyme activity in situ and the properties of intracellular organelles in general. Since cell permeabilization, particularly with chemical agents, is surprisingly easy, these techniques should find wide application for future studies.

Animals↗
PubMed1990

A double-blind, randomized comparison of fluvoxamine with mianserin in depressive illness.

The efficacy and CNS effects of the selective 5-HT re-uptake inhibitor fluvoxamine were compared with mianserin in depressed hospital out-patients in a double-blind randomized trial. Patients had to meet DSM-III criteria for Major Depressive Episode and achieve a score of at least 30 on the Montgomery-Asberg Depression Rating Scale (MADRS) after a 1-week placebo baseline period. Active treatment was for 6 weeks with an initial dose of either 100 mg fluvoxamine or 60 mg mianserin; after 1 week the dosage could be increased to 300 mg or 180 mg, respectively. Data from 63 patients (30 received fluvoxamine) were analyzed. The treatment groups were comparable with regard to age and history and severity of depression. Efficacy assessments showed similar improvements with each drug; MADRS scores improved by 65.6% with fluvoxamine and by 60.8% with mianserin. There were no significant differences between treatments at any assessment. Sedative effects were assessed using the Leeds Sleep Evaluation Questionnaire and the Digit Symbol Substitution Test. Mianserin caused a shift towards sedation in the first week in all visual analogue scales; getting to sleep and sleep quality were improved but waking was more difficult than with fluvoxamine. Similarly, the mianserin group performed less well on the Digit Symbol Substitution Test. The study confirmed that both drugs are effective treatments for depressive illness but that mianserin gives rise to sedation during the first week.

Adult↗
PubMed1990

Pharmacological elimination of tumor cells contaminating normal human bone marrow using PTT-119.

In this study, we evaluated the inhibitory effects of PTT-119, a new tripeptide which is known to be a bifunctional alkylating agent, on two tumor cell lines with different origins: SK-DHL-2 (B-cell diffuse histiocytic lymphoma cell line) and RPMI 8226 (Multiple myeloma patient cell line) and compared the toxicity of PTT-119 toward normal human bone marrow granulocyte macrophage (CFU-GM), erythroid (BFU-E), and pluripotent (CFU-GEM) progenitors. Reduction of at least four logs was achieved on clonogenic myeloma cells after 1 hr of treatment with 25 micrograms/mL of PTT-119 either in the presence or absence of irradiated bone marrow (BM) cells. More than three and at least four logs of lymphoma cell kill were found after 1 hr of incubation with 25 and 40 micrograms/mL of the tripeptide, respectively. PTT-119 antitumor effects on SK-DHL-2 were only slightly affected in the presence of an excess of BM cells. BM cells treated for 1 hr with 25 micrograms/mL of PTT-119 showed a mean recovery of 4.5, 3.8, and 13.8% of CFU-GM, BFU-E, and CFU-GEM, respectively. The addition of 5- and 10-fold excesses of red blood cells (RBC) produced a slightly higher recovery of these hematopoietic progenitors. These results suggest that PTT-119 may be useful as a chemotherapeutic agent for the ex vivo treatment of bone marrow grafts.

Antineoplastic Agents↗
PubMed1990

The effect of breastfeeding promotion on the infertile postpartum period.

A new project is testing whether a breastfeeding promotion program will change breastfeeding behavior and the length of postpartum amenorrhea. The control group and 100 of the eventual 400 experimental subjects have been recruited. The program consists of workshops, prenatal care, maternity ward postpartum care, early home visits, and a breastfeeding outpatient clinic. Early results seem to indicate decreased use of pacifiers and foods and fluids other than breast milk by women in the study group.

Breast Feeding↗