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Biomedical subjects

M Lopez

Publications and source records attributed to M Lopez.

At least 145 records · Page 8Linked to original sources
PubMed1996

Practice parameters for the diagnosis and management of immunodeficiency. The Clinical and Laboratory Immunology Committee of the American Academy of Allergy, Asthma, and Immunology (CLIC-AAAAI)

In this brief review, only the most useful immunologic tests available for defining host defects that lead to susceptibility to infection have been emphasized. It should be pointed out that those evaluations and tests ordered by the physician will rule out the vast majority of the currently recognized defects. Finally, it is important that any patients identified as abnormal by these screening tests be characterized as fully as possible in centers specializing in these diseases before therapy is initiated, since what may appear to be a simple diagnosis on the surface may be an indicator of more complex underlying problems.

Antibody Formation↗
PubMed1996

The interaction of a type A retroviral particle and class II human leukocyte antigen susceptibility genes in the pathogenesis of Graves' disease.

We have previously reported that over 85% of patients with Graves' disease have detectable serum antibodies against a human intracisternal type A retroviral particle (HIAP), which are not present in age- and gender-matched controls, suggesting a role for HIAP in triggering the autoimmune process leading to Graves' disease. To investigate the interaction of this viral particle with genetic factors, 35 members of 3 kindreds, selected because of a high family prevalence of Graves' disease (a total of 11 members affected), were examined for clinical signs of thyroid dysfunction, goiter, and opthalmopathy. Thyroid function tests and autoimmune serological profiles were also obtained. In addition, subjects were tested for the presence of antibodies against HIAP by means of immunoblot analysis of their sera, and their human leukocyte antigen (HLA) class II alleles were determined by DNA methodology. Molecular genetic analyses enabled the detection of postulated HLA susceptibility haplotypes in each family. These families had 8, 4, and 5 members, respectively, with such apparent susceptibility genes and 11, 5, and 9 members, respectively, with immunological evidence of retroviral exposure. In the presence of both factors (codetected in a total of 15 members of the 3 kindreds), the incidence of Graves' disease was 100%, 67%, and 80%, respectively. One additional member of family B and 3 in family C with both viral and genetic susceptibility factors were found to have serological abnormalities and/or goiter and ocular signs consistent with evolving or preclinical Graves' disease. In families A and C, tight linkage between HLA haplotypes and Graves' disease was demonstrated in a manner consistent with recessive inheritance. The association between the occurrence of both anti-HIAP-I antibody positivity and HLA susceptibility and the presence of Graves' disease was highly significant (P < 0.001). The pathogenesis of Graves' disease in these families appears to be attributable to the interaction between the immune response to an intracisternal type A retroviral particle and immunogenetic susceptibility, leading to the autoimmune processes that underlie Graves' disease, with subsequent development of the characteristic features of the illness. Data from these families suggest that both of these factors are necessary for final disease expression. These results imply that serological evidence of retroviral exposure together with genetic HLA susceptibility are the two major predisposing factors underlying the pathogenesis of Graves' disease. Further studies will establish whether prospective identification of persons at risk for Graves' disease is possible by this means.

Adult↗
PubMed1996

LacZ gene transfer into tumor cells abrogates tumorigenicity and protects mice against the development of further tumors.

Numerous studies have shown that the expression of immuno-stimulatory genes in tumor cells can result in the development of antitumoral immunity resulting in the rejection of the tumor cells. We show here that the simple integration and expression of the lacZ gene in the highly tumorigenic murine mastocytoma cell line P815 strongly reduces the cell's tumorigenicity. All the animals having rejected P815-lacZ challenges develop a long-lasting immunity against unmodified P815 cells with all of the animals rejecting further challenges with tumorigenic doses of P815 cells. However, this protective immunity conferred by P815-lacZ, directed against both the nuclearly expressed lacZ and surface tumor antigens, is not sufficient to act as curative immunity. In this immunogenic tumor model the expression of the lacZ antigen is more efficient than the irradiation of the cells to induce a strong immune response and an antitumoral state of vaccination in syngeneic animals.

Animals↗
PubMed1996

Ex vivo cytokine production by whole blood cells from cancer patients.

It has been hypothesized that the development of cancer might partially result from a diminution of immunocompetence. Using ex vivo cytokine production by whole blood (WB) cells after polyclonal activation, we compared cytokine production levels of cancer patients to those of healthy controls. Seventeen patients without any prior treatment and attending the hospital for oncological surgery (for cancers of several origins) were enrolled in the study. WB was collected in heparinized tubes, diluted 1/10 in RPMI 1640 and incubated for 2, 4, 24, 48, and 72 h at 37 degrees C in the presence of 5 micrograms/ml PHA and 25 micrograms/ml LPS. Cytokine levels in the supernatant were measured by specific immunoassay kits. IL-10 levels after 24 h of culture, IFN-gamma and GM-CSF levels after 24 and 72 h of culture, and LIF levels after 72 h of culture were significantly lower in cancer patients than in healthy controls. No significant difference was observed for IL-1 beta, IL-2, IL-4, IL-8, and TNF-alpha production at any culture time. Our results suggest that the putative immunosuppression of cancer patients might be reflected by their reduced production of immunostimulated cytokines.

Adult↗
PubMed1996

[Endomyocardial fibrosis with massive biventricular endocardial calcification].

Endomyocardial fibrosis is an endemic cardiac disease, characterized by the presence of fibrous tissue in the endocardium, eventually extending to the myocardium. Massive endocardial calcification of the left ventricle is a rare finding, with only a few cases reported in the literature. We reported a first case of biventricular massive endocardial calcification associated with endomyocardial fibrosis in a 22 year old woman.

Adult↗
PubMed1996

[Coronary transluminal angioplasty in octogenarians].

PURPOSE: To evaluate the immediate and long term results of percutaneous transluminal coronary balloon angioplasty (PTCA) in patients over 80 years old. METHODS: From 1/1/89 to 6/31/95, 97 patients with 80 years of age or older were submitted to PTCA and were divided into three groups: group A (GrA)-30 patients with stable angina, mean age of 82.5 years, 24 (80%) men; group B(GrB)-40 patients with unstable angina, mean age 81.2 years, 31 (77.5%) men; group C (GrC)-27 patients with myocardial infarction (MI), mean age of 82 years, 16 (59.2%) men. RESULTS: Early outcome-general success rate of 84.5% and mortality rate of 5.1%. The success and mortality rate were in GrA 83.3% and 3.3%, in GrB 85% and 5% and in GrC 85.2% and 7.4%, respectively. Late outcome-the number and percentage of patients with late follow-up and the clinic-angiographic and angiographic restenosis rates were for GrA 19(76%), 52.9%, 75%; GrB 30(88.2%), 30.8%, 61.5% and GrC 12(52.2%), 66.6%, 85.7%, respectively. CONCLUSION: PTCA can be considered an important revascularization alternative in octogenarian patients because of high early success rate, low mortality and acceptable long-term outcome.

Aged↗
PubMed1996

Blood group polymorphisms in the Canary Islands.

Human samples from the seven Canary Islands were studied for the following polymorphic red cell blood group systems: ABO, RH, MNSs, FY and P. In contrast to the intra-insular homogeneity found, inter-insular heterogeneity was observed for ABO, RH and FY. The observed blood group allelic systems were within the range of European populations, with some minor African contribution.

ABO Blood-Group System↗
PubMed1996

Tumoricidal potential of human macrophages grown in vitro from blood monocytes.

Adoptive transfer of activated autologous human macrophages obtained by in vitro differentiation of monocytes in culture has successfully undergone phase I clinical trials in patients with metastatic cancer. The efficacy of these autologous macrophages in the in vivo killing of human tumors has now to be demonstrated. GM-CSF was shown to increase the number of monocytes differentiating in culture into macrophages. These were then activated with IFN gamma which was reported as the best cytokine for tumoricidal activation of macrophages. The aim of this paper was to evaluate the in vitro tumoricidal activity of macrophages grown with GM-CSF and IFN gamma. This tumoricidal function was investigated by measurement of the cytolytic (chromium-51 release assay), cytostatic (anti-proliferative activity as measured by inhibition of [3H]-thymidine incorporation in two different assays) and cytotoxic (MTT assay) activities on two tumor cells lines, U937 and K562 (respectively highly sensitive and resistant to soluble TNF alpha). Our results demonstrated that GM-CSF-grown macrophages exhibited significant cytolytic, cytotoxic and cytostatic activities on U937 cells. These were partly enhanced by IFN gamma activation. In contrast, they had no lytic and lower cytotoxic and cytostatic activities on K562 cells, and these were not modified by IFN gamma activation. Our data provide valuable information for future in vivo studies using adoptively transferred autologous macrophages.

Adoptive Transfer↗
PubMed1995

The human PRR2 gene, related to the human poliovirus receptor gene (PVR), is the true homolog of the murine MPH gene.

Until now it was assumed that the murine poliovirus (PV) receptor homolog gene (MPH) had been identified. Alternative splicing of MPH transcripts generates two glycoproteins named MPH alpha and MPH beta which share an identical N-terminal region composed of three immunoglobulin (Ig)-like domains and different C-terminal regions. Using a degenerate PCR strategy, we describe the identification of a second human PVR-related gene (PRR2), which encodes two glycoproteins, PRR2 alpha (short form) and PRR2 delta (long form). They present 69 and 73% identity with MPH alpha and MPH beta, respectively. In contrast, the human PVR protein exhibits 51% identity which is moreover restricted to the three Ig domains of the murine protein. We therefore propose that PRR2, and not PVR, is the true human homolog of MPH. In addition, Northern blot analysis showed that two mRNA isoforms of 3.0 kb (PRR2 alpha) and 4.4 kb (PRR2 delta) are ubiquitously found in various normal human tissues. In situ hybridization allowed us to map PRR2 to the 19q13.2-q13.4 bands of the human genome, in the same chromosomal region as PVR.

Alternative Splicing↗
PubMed1995

Complementary DNA characterization and chromosomal localization of a human gene related to the poliovirus receptor-encoding gene.

The human poliovirus (PV) receptor (PVR) is a member of the immunoglobulin (Ig) superfamily with unknown cellular function. We have isolated a human PVR-related (PRR) cDNA. The deduced amino acid (aa) sequence of PRR showed, in the extracellular region, 51.7 and 54.3% similarity with human PVR and with the murine PVR homolog, respectively. The cDNA coding sequence is 1.6-kb long and encodes a deduced 57-kDa protein; this protein has a structural organization analogous to that of PVR, that is, one V- and two C-set Ig domains, with a conserved number of aa. Northern blot analysis indicated that a major 5.9-kb transcript is present in all normal human tissues tested. In situ hybridization showed that the PRR gene is located at bands q23-q24 of human chromosome 11.

Amino Acid Sequence↗
PubMed1995

Preparation and successful engraftment of purified CD34+ bone marrow progenitor cells in patients with non-Hodgkin's lymphoma.

From September 1992 to January 1994, we evaluated the use of the CEPRATE SC stem cell concentrator (CellPro, Inc, Bothell, WA) to select CD34+ cells from the bone marrow (BM) of 25 patients with non-Hodgkin's lymphoma in complete remission. This system uses the biotinylated 12.8 IgM MoAb to select CD34+ cells. Cells are retained on an avidin column and detached by agitation. Fifteen patients have been transplanted with the CD34+ purified fraction. The CD34+ purified fraction of the 25 processed BMs contained a median of 0.54% of the original nucleated cells in a volume of 5 to 10 mL. The median concentration of CD34+ cells was 49% (range, 12% to 80%), and the median enrichment of CD34+ cells was 33-fold (range, 9- to 85-fold). This selected CD34+ fraction retained 60% (range, 15% to 95%) of late granulocyte-macrophage colony-forming units (CFU-GM), 55% (range, 12% to 99%) of early CFU-GM, and 31% (range, 2% to 100%) erythroid burst-forming units (BFU-E) corresponding to median enrichments of 22-fold (range, 1- to 71-fold), 19-fold (range, 2- to 58-fold), and 14-fold (range, 2- to 200-fold), respectively. There was a correlation between immune phenotypes and progenitor cells. In the initial buffy-coat fractions, the percentage of CD34+ cells was correlated to the cloning efficiency of both late CFU-GM (P < .05) and early CFU-GM (P < .001). In the final selected fraction, there was a correlation between the percentage of CD34+/CD33- and the cloning efficiency of early CFU-GM (P < .05) and between the percentage of CD34+/CD33+ and the cloning efficiency of late CFU-GM (P < .05). Lymphoma cells positive for t(14; 18) were found by polymerase chain reaction in 9 of 14 buffy coats tested before CD34+ cell purification. In 8 cases, the CD34(+)-selected fraction was found to be negative, and the CD34- fraction was found to be positive. After cryopreservation, the recoveries of progenitor cells in the CD34(+)-purified fraction were 79% for late CFU-GM, 71% for early CFU-GM, and 73% for BFU-E. The 15 patients transplanted with the concentrated CD34+ fraction received a median dose of 1 x 10(6) CD34+ cells/kg (range, 0.3 to 2.96) and 10.62 x 10(4) early CFU-GM/kg (range, 0.92 to 25.55). Median days to recovery to 0.5 x 10(9)/L neutrophils and 50 x 10(9)/L platelets were days 15 (range, 10 to 33) and 23 (range, 11 to 68), respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Creation of a volume lesion in the dog prostate using neodymium:YAG laser coagulation: concepts for clinical treatment.

BACKGROUND AND OBJECTIVE: The purpose of this study was to determine the geometrical development of a coagulated zone in the canine prostate during free beam side fire Nd:YAG laser coagulation. STUDY DESIGN/MATERIALS AND METHODS: A series of 10 male dogs underwent endoscopic prostatic Nd:YAG fixed position laser coagulation through a suprapubic cystotomy using a right-angle deflecting delivery catheter (Microvasive, Boston, MA) at times varying from 10 to 120 seconds at 30 watts. In addition, two dogs underwent lasing by pulling the catheter at 1 mm/s in four quadrants. Acute gross and microscopic pathology specimens were prepared and the lesion shape and volume determined. RESULTS: Analysis of the coagulated volume showed that during the initial 15 seconds of lasing, the zone of coagulation approximates a sphere centered on the urothelium opposite the laser fiber. However, as lasing progressed, the lesion changed from a sphere to an expanding ellipse. This changing geometry can be explained by the absorption and scatter characteristics of the laser and the temperature equilibrium that is established within the prostate. CONCLUSION: An understanding of this time-dependent geometrical shift from a sphere to an ellipse allows the surgeon to supplement the fixed protocols for lasing at certain positions for given amounts of time. Specific plans can then be established for tissue at the bladder neck, apex, anterior stroma, floor, and irregular prostatic regrowth.

Absorption↗
PubMed1995

Immune depression induced by protein calorie malnutrition can be suppressed by lesioning central noradrenaline systems.

Depressed immune function is well documented in protein calorie malnutrition (PCM). Also, central noradrenergic hyperactivity has recently been reported in malnourished animals. Increase in central noradrenaline activity could be responsible for cell-mediated immune depression. The present study is designed to address this hypothesis by testing whether neurotoxic lesion of central noradrenergic systems by 6-hydroxydopamine (6-OHDA) could improve lymphoproliferative response to mitogens and interleukin (IL)-1 production in PCM rats. A significant enhancement of lymphoproliferative response to concanavalin A (ConA) and in IL-1 production was observed in spleen mononuclear cells of PCM rats injected intracerebroventricularly with 120 micrograms of 6-OHDA, as compared with solvent injected and untreated PCM animals. A significant decrease in brain noradrenaline levels was produced in the drug-injected animals. These results suggest that central noradrenergic hyperactivity is one of the mechanisms involved in the immunodepression produced by malnutrition.

Animals↗
PubMed1995

Intrapatient comparison of single-agent epirubicin with or without lonidamine in metastatic breast cancer.

The aim of this study was to determine if lonidamine (LND) supplementation to single-agent epirubicin (EPI) could reverse anthracycline resistance in patients with metastatic breast cancer. 45 patients with metastatic breast cancer were treated with EPI 120 mg/m2 by intravenous (i.v.) bolus every 3 weeks. Patients who progressed were given the same chemotherapy regimen on day 4 in combination with oral LND, 150 mg on day 1, 300 mg on day 2 and 450 mg on days 3-5. Among the 40 evaluable patients, 6 complete responses (CR) and 14 partial responses (PR) were achieved with EPI treatment alone for an overall response rate of 50%. The median duration of response was 6.5 months. Among the 25 patients treated with EPI+LND, 5 PR (21% of 24 evaluable patients) were observed with a median duration of response of 7 months. The median survival in patients receiving both treatments was 20 months. The survival for all patients was 18 months. The survival of patients receiving LND was not significantly longer than for the other patients. Myelotoxicity was the most common side-effect followed by alopecia, nausea and vomiting, and stomatitis. LND-related toxic effects were mild-to-moderate epigastralgia and myalgia. Anthracycline-related toxicity was the same in the two treatment groups. This study indicates that LND may circumvent clinical resistance to EPI without altering the pattern or severity of the toxicity of this anthracycline. Continued investigation of the clinical modulation of EPI resistance by LND in breast cancer is warranted, hopefully in patients with known multidrug resistance status.

Adult↗
PubMed1995

Sequential chemoimmunotherapy for advanced non-small cell lung cancer using cisplatin, etoposide, thymosin-alpha 1 and interferon-alpha 2a.

A phase II study was performed to evaluate the clinical and immunological effects of a regimen of cisplatin (DDP) and etoposide (VP-16) combined with thymosin-alpha 1 (TA1) and low-dose interferon-alpha 2a (IFN) in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Chemoimmunotherapy cycles were repeated every 3 weeks. There were 24 responses (two complete, 22 partial) among 56 assessable patients. Median survival was 12.6 months. Overall, treatment was well tolerated. Natural killer cell activity and lymphocyte subtypes were depressed by chemotherapy, but this effect was less prominent in patients receiving TA1 and IFN in comparison with a concomitant group of patients treated with DDP and VP-16 only. The combination of DDP and VP-16 and TA1 and IFN is effective in advanced NSCLC with acceptable toxicity. However, the results of this study need to be confirmed in a randomised trial.

Adult↗
PubMed1995

Identification of important allergens in German cockroach extracts by sodium dodecylsulfate-polyacrylamide gel electrophoresis and western blot analysis.

BACKGROUND: Despite recent advances in the purification and characterization of cockroach allergens, identification of clinically important allergens and their source have not been completely elucidated. This study investigated the allergen content of German cockroach (Blattella germanica) whole body (GWBE) and fecal (GFE) extracts. METHODS: Sera from 37 subjects with asthma, with positive skin test results to cockroach, were used for RAST and Western blot (after sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE] under reducing conditions); this serum panel is the largest used to date for cockroach allergen analysis. RESULTS: RAST reactivity to GWBE and GFE were highly correlated (r = 0.882, p < 0.001). SDS-PAGE and Western blotting showed that GWBE and GFE had similar patterns of IgE binding. Furthermore, Western blot inhibition investigations revealed that either GWBE or GFE could almost completely inhibit the reactivity of the other extract, SDS-PAGE and Western blotting demonstrated in both extracts numerous bands that displayed a high prevalence of IgE binding. Protein bands at 67, 50, 45, and 36 kd bound more than 50%, and the band at 60 kd bound approximately 80% of the sera tested. CONCLUSIONS: In summary, this investigation identified German cockroach allergens, established their relative importance by prevalence of reactivity to a large serum panel, and demonstrated that cockroach feces possess significant allergenic activity. Five allergens identified demonstrated reactivity with up to 50% to 80% of the 37 subjects' sera tested.

Allergens↗