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Biomedical subjects

M Lopez

Publications and source records attributed to M Lopez.

At least 181 records · Page 10Linked to original sources
PubMed1994

Further characterization of CD82/IA4 antigen (type III surface protein): an activation/differentiation marker of mononuclear cells.

The mononuclear cell surface protein IA4 was originally identified in our lab using a mAb selected because of its strong reactivity with three lymphoblastoid variant cell lines which are HLA class I deficient, are LAK susceptible, and form a high number of conjugates with LAK effectors. We previously cloned the cDNA of the IA4 protein, coding for a 267-amino-acid type III integral membrane protein, with four transmembrane domains and three possible N-glycosylation sites. The IA4 protein belongs to the tetra span transmembrane (TST) new family of surface molecules, which also includes CD9, CD37, CD53, CD63, and TAPA-1. IA4 antigen was recently recognized as belonging to a new cluster of differentiation CD82 (International CD Workshop, Boston 1993). The IA4 antigen expression pattern at the surface of immune cells from normal donors was studied. On T lymphocytes, IA4 was barely detectable on resting cells and increased 3.5- to 7-fold following PHA or PHA+PMA stimulation. This IA4 increased expression is correlated with the morphologic change in blast cells and with the expression of activation markers such as CD2 and MHC class II antigens, therefore suggesting that IA4 is an activation marker on T lymphocytes. The expression of IA4 was low on circulating resting monocytes collected by elutriation. However, these monocytes, cultured in medium alone or with GM-CSF, acquired the morphology of macrophage and simultaneously overexpressed MHC Class II, CD14, and IA4 antigens, suggesting that IA4 is a differentiation marker for macrophages, whatever the culture conditions, either adherent (plastic culture dishes) or nonadherent (Teflon culture bags). IA4 stable transfectants of the murine mastocytoma cell line P815 were obtained and used to generate a new mAb. Competitive epitope binding studies have shown that IA4 antigen presents a dominant epitope recognized by most of the mAb prepared either in our lab or elsewhere. This dominant epitope is not shared by any of the other antigens of the TST family. Using this new mAb we were able to biochemically characterize the IA4 antigen as a 28-kDa protein, highly N-glycosylated with different patterns on various cells.

Animals↗
PubMed1994

An ELISA for the measurement of human leukemia inhibitory factor in biological fluids and culture supernatants.

A new monoclonal antibody-based ELISA for leukaemia inhibitory factor/human interleukin for DA cells (LIF/HILDA) measurements is described. The sensitivity (56 pg/ml after 4 h incubation, 14 pg/ml after 24 h incubation), precision (intra-assays < 5%), reproducibility (interassay < 10%), and accuracy (recoveries, ranging between 98 and 119%, in several fluids) of the assay, plus its excellent performance in dilution tests, and the lack of interference when in the presence of possible cross-reactive substances guarantee accurate cytokine measurement in biological fluids such as serum, plasma, synovial fluid, follicular fluid, urine and culture supernatants. Using the assay, LIF/HILDA was measurable in supernatants after in vitro whole blood stimulation with phytohemagglutinin (PHA), OKT3, and phorbol myristate acetate (PMA) but not with lipopolysaccharide (LPS) or Ca ionophore. LIF/HILDA production was not measurable until after 24 h of culture, when cytokine levels were seen to increase linearly in the supernatant to reach values of up to 40 ng/ml after 96 h of culture. Finally, a good correlation was found (r = 0.96; p < 0.0001; y = 23.1x + 233) between the LIF/HILDA values obtained using the ELISA and DA-1a bioassay.

Adult↗
PubMed1994

Adjuvant therapy of colorectal cancer.

PURPOSE: This review was undertaken to examine the evidence of the effectiveness of adjuvant chemotherapy in colorectal cancer. METHODS: Published studies were reviewed and analyzed. RESULTS: For over three decades, a large series of adjuvant systemic trials have been conducted in carcinoma of the colon and rectum in an attempt to reduce recurrence and ultimately improve survival. However, only in the last few years have significant gains been made. In colon cancer with regional nodal metastasis, combined treatment with 5-fluorouracil and levamisole has resulted in significant reduction of tumor recurrence and improved survival. In rectal cancer, combined modality treatment with radiotherapy and chemotherapy is considered the standard for care by many investigators, although numerous questions remain unanswered. CONCLUSIONS: The existing evidence suggests that adjuvant therapy may be of value in selected patients with colorectal cancer. Several currently active trials are pursuing very hopeful leads, and clinicians are encouraged to enter their patients on available trials.

Chemotherapy, Adjuvant↗
PubMed1994

Neurotoxicity of antitumoral IL-2 therapy: evoked cognitive potentials and brain mapping.

Antitumoral interleukin-2 (IL-2) therapy is frequently associated with a neurotoxicity that manifests itself in neuropsychiatric disturbances and, more rarely, with neurological focal signs. With the aim of documenting the involvement of cognitive functions after IL-2 treatment, we studied 20 patients using evoked cognitive potentials (P300) and computer analysis of the EEG signal. A comparison of the tests performed before and after the subcutaneous infusion of IL-2 showed a significant lengthening in mean P300 latencies and a percentage increase in the EEG frequencies contained with the delta and theta bands, especially in the frontal regions.

Adult↗
PubMed1994

Use of Norplant implants in a New York City clinic population.

Two-hundred-eight women attending family planning clinics in New York City who received the Norplant contraceptive system during the first sixteen months of Norplant implants insertions were evaluated. Within this clinic population, Norplant implants were a popular contraceptive choice and were removed from 64 of the 208 recipients. Reasons for removal included bleeding, weight gain, and headache, and were consistent with those found in the clinical trials. Prior satisfaction with oral contraceptives did not predict success or failure with Norplant implants. The rate of follow-up visits to the family planning clinics was low. However, evidence exists that these women did not lose contact with the medical center and continued to receive health care.

Adult↗
PubMed1994

Cytokines and organ transplantation. A review.

Cytokines regulate both aspecific inflammatory responses and specific immune responses. Inflammatory changes occur in the organ transplant as a result of tissue trauma and ischemia/reperfusion in the organ donor and at the time of transplant operation. There is a possibility that cytokines play a role in mediating theses changes. These aspecific inflammatory changes may not only affect graft function but also influence graft immunogenicity (enhanced MHC and adhesion molecule expression) and thus, vulnerability to rejection. Cytokines orchestrate the specific immune response elicited by organ transplantation. Relevance of cytokines to the rejection reaction is multifactorial in nature: 1) promotion of the proliferation an differentiation of specific alloreactive T and B cells clones and differentiation and activation of CTL and NK cells, 2) chemotactic effect and induction of the expression of adhesion molecules, 3) enhancement of MHC class I and II expression, and 4) direct cytotoxic effect on the target grafted cells. Therefore, modulation of cytokine activity either specifically (monoclonal antibody, soluble receptor, etc.) or aspecifically (cyclosporin, FK 506, Rapamycin, steroids, etc.) is essential in controlling graft rejection. Determination of circulating cytokines and cytokines measurement within the biological fluids produced by an organ transplant may help in the diagnosis of rejection episodes and other complications following organ transplantation.

Antibody Formation↗
PubMed1994

Retroviral transfer of the nlsLacZ gene into human CD34+ cell populations and into TF-1 cells: future prospects in gene therapy.

Few data are available concerning behavior of reimplanted human hematopoietic cells after autologous stem cell transplantation. This paper reports the possibility to transfer gene markers coding for beta-galactosidase (beta-Gal) activity by retroviral vectors into a human leukemic growth factor-dependent cell line, TF-1, and into human hematopoietic progenitors isolated from peripheral blood or bone marrow. Using various combinations of retroviral vectors and packaging cell lines, we demonstrated high expression of a bacterial beta-Gal activity induced by the LacZ gene, the nlsLacZ gene, or the Sh-ble/LacZ gene, in human hematopoietic cells. The expression of the nlsLacZ construct was stable until the end of the culture in infected CD34+ cell-enriched cell populations, and a slow decrease of transgene expression was observed in a transduced TF-1 cell population during a 1-year long-term culture. Data obtained with the nlsLacZ gene demonstrate that both retroviral transfer and corresponding gene expression were not found to modify the pattern of cell proliferation and differentiation. These results open interesting prospectives for the use of the nlsLacZ gene to mark and follow the fate of progenitor cells isolated from patients with cancers prior to reimplantation.

Animals↗
PubMed1994

Biochemotherapy with thymosin alpha 1, interleukin-2 and dacarbazine in patients with metastatic melanoma: clinical and immunological effects.

BACKGROUND: DTIC and interleukin-2 (IL-2), as single agents, have a limited anti-tumor activity in patients with metastatic melanoma. Experimentally, thymosin alpha 1 (TA1) may modulate the action of IL-2. We investigated the clinical and immunological effects of a combination with these three agents. PATIENTS AND METHODS: Forty-six patients with measurable metastatic melanoma were treated with DTIC 850 mg IV on day 1, TA1 2 mg s.c. on days 4 to 7, and IL-2 18 MU/m2/d by continuous intravenous infusion on days 8 to 12. Cycles were repeated every 3 weeks. RESULTS: Objective responses were obtained in 15 (36%) of 42 evaluable patients (CI at 95%: 22%-50%). Two patients experienced complete responses, and stable disease was observed in five. The median time to progression was 5.5 months and median survival was 11 months. Side effects were predominantly caused by IL-2. Treatment was tolerated reasonably well, and there was no overlapping toxicity or interference between chemotherapy and biotherapy. Baseline sCD4 levels seem to correlate to tumor burden. Patients benefiting from treatment had lower sCD4 and higher sCD8 than did progressing patients. CONCLUSIONS: The combination of DTIC + TA1 + IL-2 is active in the treatment of advanced melanoma, with acceptable toxicity. However, even more active regimens are needed, and the interactions between thymic hormones and cytokines should be further explored.

Adult↗
PubMed1994

Rate and gender dependence of the sweating, vasoconstriction, and shivering thresholds in humans.

BACKGROUND: The range of core temperatures not triggering thermoregulatory responses ("interthreshold range") remains to be determined in humans. Although the rates at which perioperative core temperatures vary typically range from 0.5 to 2 degrees C/h, the thermoregulatory contribution of different core cooling rates also remains unknown. In addition, sweating in women is triggered at a slightly greater core temperature than in men. However, it is unknown whether the vasoconstriction and shivering thresholds are comparably greater in women, or if women tolerate a larger range of core temperatures without triggering thermoregulatory responses. Accordingly, the authors sought to (1) define the interthreshold range; (2) test the hypothesis that, at a constant skin temperature, the vasoconstriction and shivering thresholds are greater during rapid core cooling than during slowly induced hypothermia; and (3) compare the sweating, vasoconstriction, and shivering thresholds in men and women. METHODS: Eight men and eight women participated. The men participated on 2 separate days; no anesthesia or sedatives were administered. On each day, they were cutaneously warmed until sweating was induced and then were cooled by a central venous infusion of cold fluid. The cooling rates were 0.7 +/- 0.1 degrees C/h on 1 day and 1.7 +/- 0.4 degrees C/h on the other, randomly ordered. Skin temperature was maintained near 36.7 degrees C throughout each trial. The women were studied only once, in the follicular phase of their menstrual cycles, at the greater cooling rate. RESULTS: The interthreshold range was approximately 0.2 degrees C in both men and women, but all thermoregulatory response thresholds were approximately 0.3 degrees C higher in women. All thresholds were virtually identical during slow and fast core cooling. CONCLUSIONS: Our findings confirm the existence of an interthreshold range and document that its magnitude is small. They also demonstrate that the interthreshold range does not differ in men and women, but that women thermoregulate at a significantly higher temperature than do men. Typical clinical rates of core cooling do not alter thermoregulatory responses.

Adult↗
PubMed1994

Thallium-201 scintigraphy and chemotherapeutic response in rhabdomyosarcoma.

Thallium-201 scintigraphy was used to evaluate chemotherapeutic response in a case of rhabdomyosarcoma treated with epirubicin. A scintigraphic semiquantitative index of tumor viability was correlated with MRI and clinical assessment. Both imaging studies were performed before therapy and after treatment involving a cumulative dose of 640 mg/m2 of epirubicin. A very good inverse correlation was observed between Tl-201 uptake and tumor necrosis evaluated by MRI, leading to the conclusion that sequential Tl-201 scintigraphy may have a role not only in delineating the extent of the tumor, but in objectively assessing tumor response to therapeutic interventions. The proposed scintigraphic method is much simpler to perform and less expensive than MRI-derived semiquantitative measurement of tumor necrosis.

Adult↗
PubMed1994

Immunocytochemical diagnosis of amelanotic metastatic melanoma using monoclonal antibodies HMB-45 and Ep1-3.

The analysis of fine-needle aspirates and effusions has proved to be a valuable tool for the cytological identification of metastatic melanoma. Nevertheless, while malignant pigmented cells can be easily detected on cytological specimens, their identification may be very difficult in patients bearing amelanotic lesions. In the present study we have evaluated whether this limitation can be overcome using two monoclonal antibodies (mAbs) HMB45 and Ep1-3, which are highly specific for the melanocyte lineage. These reagents were assayed in immunocytochemical tests performed on cytological material obtained from 50 patients with a past history of melanoma and 463 bearing metastases from a cryptic primary tumour. These mAbs, employed in combination with a panel of monoclonal reagents with well-defined tumour specificity, may improve the accuracy of the conventional cytopathological diagnosis of melanoma metastases in the two groups of patients.

Antibodies, Monoclonal↗
PubMed1994

Prevalence of basidiomycete allergy in the USA and Europe and its relationship to allergic respiratory symptoms.

A total of 701 adults living in the USA or Western Europe who had symptoms of allergic respiratory disease were skin prick tested with extracts prepared from eight basidiomycetes species and four Fungi Imperfecti species. In these subjects, the presence of asthma, rhinitis, or both was determined by questionnaire. Overall, 178/701 (25.4%) of the participants reacted to at least one basidiomycete extract. There was no difference in the prevalence of reactivity detected in the USA and Europe (P < 0.005); however, the prevalence of reactors in individual centers from both areas varied significantly. Psilocybe cubensis was the most potent allergen source in both the USA (12.3% reacted) and Europe (16.0%). Pleurotus ostreatus was second overall (10.6%) and in the USA (10.7%), and third in Europe (10.3%). Pisolithus tinctorius and Coprinus quadrifidus produced the least potent allergens, with only 5.4% of the population reacting. There was a significant relationship (P < 0.005) between basidiospore reactivity and the presence of atopy, asthma, and asthma and rhinitis. Basidiospore reactivity was not associated with the presence of rhinitis alone (P = 0.312). These results suggest that basidiomycetes are important sources of aeroallergens in geographically disparate regions and may be particularly important in patients with asthma.

Adult↗
PubMed1994

ERP, a new member of the ets transcription factor/oncoprotein family: cloning, characterization, and differential expression during B-lymphocyte development.

The ets gene family encodes a group of proteins which function as transcription factors under physiological conditions and, if aberrantly expressed, can cause cellular transformation. We have recently identified two regulatory elements in the murine immunoglobulin heavy-chain (IgH) enhancer, pi and microB, which exhibit striking similarity to binding sites for ets-related proteins. To identify ets-related transcriptional regulators expressed in pre-B lymphocytes that may interact with either the pi or the microB site, we have used a PCR approach with degenerate oligonucleotides encoding conserved sequences in all members of the ets family. We have cloned the gene for a new ets-related transcription factor, ERP (ets-related protein), from the murine pre-B cell line BASC 6C2 and from mouse lung tissue. The ERP protein contains a region of high homology with the ETS DNA-binding domain common to all members of the ets transcription factor/oncoprotein family. Three additional smaller regions show homology to the ELK-1 and SAP-1 genes, a subgroup of the ets gene family that interacts with the serum response factor. Full-length ERP expresses only negligible DNA-binding activity by itself. Removal of the carboxy terminus enables ERP to interact with a variety of ets-binding sites including the E74 site, the IgH enhancer pi site, and the lck promoter ets site, suggesting a carboxy-terminal negative regulatory domain. At least three ERP-related transcripts are expressed in a variety of tissues. However, within the B-cell lineage, ERP is highly expressed primarily at early stages of B-lymphocyte development, and expression declines drastically upon B-cell maturation, correlating with the enhancer activity of the IgH pi site. These data suggest that ERP might play a role in B-cell development and in IgH gene regulation.

3T3 Cells↗
PubMed1994

Selection of patients with monoclonal gammopathy of undetermined significance is mandatory for a reliable use of interleukin-6 and other nonspecific multiple myeloma serum markers.

Serum levels of various immunochemical markers of clinical interest, as interleukin-6 (IL-6), C-reactive protein (CRP) and beta 2-microglobulin (beta 2M), were measured in sera from 98 subjects affected with monoclonal gammopathy of undetermined significance (MGUS; 80% of which bearing cancer too) and from 39 patients with multiple myeloma (MM). In addition, the ratio between serum IgG/IgA amounts (GAR) was also calculated in monoclonal gammopathies of IgG type. Consistent with our previous investigations, we found that tumor presence significantly influenced the serum levels of the various markers (except GAR) in MGUS patients; in fact, only when comparing MGUS without tumor and MM patients, was a clear difference observed for all markers considered. The data presented discourage the use of IL-6, CRP and beta 2M as discriminant indices between MGUS and MM patients, unless a careful selection of MGUS subjects is performed. Further investigations on these potential markers are therefore needed for a more rational clinical application.

Adult↗
PubMed1994

[Informed consent, what information is left after a therapeutic trial?].

In order to evaluate the outcome of information given to patients included in a therapeutic trial after having signed a consent form, 77 patients (68 men, 9 women with an average age of 57.9 years) included in the IMPACT study (multicenter, randomised, double-blind protocol, the main objective of which was to assess the antiarrhythmic effect of oral administration of delayed action mexiletine in patients with a recent myocardial infarction), answered a questionnaire of 85 items. The quantity and degree of comprehension of the recalled information at the end of the trial were appreciated from the replies to 13 questions based on the definition or understanding of the most important details of the consent form and on a comprehension score with a maximum value of 14 points. The global quantity of information recalled after an interval ranging from 5 to 21 months was estimated at 60% of the information provided but the recall was not uniform according to the different elements of the consent form: the aim of the study, the concept of placebo, the nature of the active treatment, the randomisation and possible side effects were only correctly apprehended by 40 to 50% of patients: the type of patient included, the duration of the trial, the content of the gelules, the division between treatment/placebo and the concept of double-blind were known to 50 to 75% of participants: the sites of the test centres, the possibility of unmasking the "blind" are of withdrawing from the trial were correctly understood in 75 to 90% of cases. The global average comprehension score was 8.7.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗