Use and interpretation of diagnostic immunologic laboratory tests.
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B-Lymphocytes↗
Biomedical subjects
M Lopez
Publications and source records attributed to M Lopez.
Carboplatin, methotrexate, and vinblastine in patients with bladder cancer who were ineligible for cisplatin-based chemotherapy.
BACKGROUND: A Phase II trial with a new regimen of methotrexate, carboplatin, and vinblastine (M-CAVI) was conducted for patients with bladder cancer who could not receive cisplatin-based chemotherapy. METHODS: Treatment consisted of methotrexate (30 mg/m2) on days 1, 15, and 22; carboplatin (300 mg/m2) on day 2; and vinblastine (3 mg/m2) on days 2, 15, and 22, scheduled at 28-day intervals. The dosage of carboplatin was adjusted for creatinine clearance. Twenty-five patients with metastatic (n = 9) or locally advanced or locoregional bladder cancer with a poor prognosis (n = 16) were treated with M-CAVI. Fifteen patients had abnormal serum creatinine levels, 4 had a low performance status, 3 had cardiac disease, and 3 were older than 70 years old. RESULTS: Among 23 patients assessable for clinical response, the response rate was 48%. The median duration of response for metastatic disease was 7 months. Among nine patients assessable for pathologic response, there were two complete responses and three partial responses. The toxic effects have been moderate. CONCLUSIONS: M-CAVI is an active and well-tolerated regimen that can be used in patients with bladder cancer who are ineligible to receive cisplatin-based chemotherapy.
Adult↗
Multiple Rh messenger RNA isoforms are produced by alternative splicing.
Three Rh-related cDNAs have been isolated from a human bone marrow cDNA library and by polymerase chain reaction (PCR) amplification of human bone marrow and erythroblast mRNAs. They potentially encode a family of Rh protein isoforms that exhibit several unexpected structural properties as compared with the Rh polypeptide encoded by the cDNA clone identified previously. These modifications include several peptide deletions, the predicted alteration of Rh protein topology within the cell membrane, variations in the number and surface exposition of cysteine residues, and the generation of new C-terminal polypeptide segments caused by frameshift mutations. The four Rh mRNAs now described correspond to different splicing isoforms transcribed from the same Rh gene, and all exist in the same cell lineage (erythroid). Moreover, PCR experiments indicated that at least three of these RNA species exist in reticulocytes from donors with different commonly expressed Rh phenotypes. Although the translated proteins have not yet been characterized, these results suggest that the two genes at the RH locus may direct the synthesis of several protein species possibly corresponding to different Rh antigenic variants.
Amino Acid Sequence↗
[Implantable site used for access to blood in chronic hemodialysis. Preliminary trials].
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Cardiac Catheterization↗
[Severe respiratory syncytial virus pneumonia following bone marrow autograft. 3 cases].
Three patients developed severe respiratory syncytial virus pneumonia after bone marrow autograft for acute leukaemia. Clinically, the disease presents as interstitial or bilateral alveolo-interstitial pneumonia with hypoxaemia. Signs of ENT infection (otitis media, sinusitis) are present in 30 percent of the cases. In all 3 patients, the syncytial virus was isolated by direct immunofluorescence in bronchoalveolar lavage fluid. In 2 patients the infection began soon after the autograft, in deeply aplastic subjects, and required intubation and assisted ventilation. These 2 patients died despite inhalation of aerosolized ribavirin combined, in one of them, with ribavirin injections. In the third patient the infection began some time after the autograft and responded well to ribavirin in aerosols. In these three cases the viral infection occurred in an epidemic and nosocomial context. The respiratory syncytial virus is usually transmitted by the hands. Owing to the severity of this infection with lung involvement in immunodepressed patients, specific prophylactic measures should be taken side by side with the conventional measures.
Administration, Inhalation↗
Direct stimulation of cytokines (IL-1 beta, TNF-alpha, IL-6, IL-2, IFN-gamma and GM-CSF) in whole blood: II. Application to rheumatoid arthritis and osteoarthritis.
Rheumatoid arthritis (RA) is an immune disease in which the pathological immune reaction is thought to be initiated by the presentation of an (auto) antigen or superantigen by MHC class II positive cells to CD4 T cells. These successive immunological events can be studied by the cytokines produced at the different stages. Cytokine secretion by stimulated cells in autologous diluted whole blood has allowed the study of the immune profile characteristic of rheumatoid arthritis. The pattern of RA patient whole blood cells cultured in autologous blood is characterized by hyperactivity of the mononuclear cells with high secretion of IL-1 beta, TNF-alpha and IL-6 and low production of IFN-gamma, in comparison with the normal (N) and osteoarthrosis (OA) populations. The IL-2 secretion pattern is unique, arising from production followed by consumption. This production-consumption turnover is the most elevated in the RA group. The T cells are indeed activated in rheumatoid arthritis but regulatory events suppress some of their functions. A correlation was found between the inflammatory proteins and mediators of cellular immunity and macrophagic function: IL-1 beta and the sedimentation rate; IL-6 and fibrinogen; TNF-alpha and the number of blood monocytes. The secretion of OA-stimulated whole blood cells was similar to RA for two monokines (overproduction of TNF-alpha and IL-6) and different for IL-1 beta, not different from normal in OA. Stimulated whole blood cell cytokine secretion profile from RA and OA groups, was the same as previously observed in synovial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Direct stimulation of cytokines (IL-1 beta, TNF-alpha, IL-6, IL-2, IFN-gamma and GM-CSF) in whole blood. I. Comparison with isolated PBMC stimulation.
Production of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), interferon gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) after stimulation by lipopolysaccharide (LPS) and phytohemagglutinin (PHA) was studied in 1/10 diluted whole blood (WB) culture and in peripheral blood mononuclear cell (PBMC) culture. Cytokines IL-1 beta, TNF-alpha and IL-6 are preferentially stimulated by LPS whereas IL-2, IFN-gamma and GM-CSF are stimulated by PHA. Combination of 5 micrograms/ml PHA and 25 micrograms/ml LPS gave the most reliable production of the six cytokines studied. IL-1 beta, TNF-alpha and IL-6 represent a homogeneous group of early-produced cytokines positively correlated among themselves and with the number of monocytes in the culture (LeuM3). Furthermore, IL-1 beta was negatively correlated with the number of T8 lymphocytes. IL-2, IFN-gamma and GM-CSF represent a group of late-produced cytokines. Kinetics and production levels of IL-6 and GM-CSF are similar in WB and PBMC cultures. In contrast, production levels of TNF-alpha and IFN-gamma are higher in WB than in PBMC whereas production levels of IL-6 and IL-2 are lower in WB than in PBMC. Individual variation in responses to PHA + LPS was always higher in PBMC cultures than in WB cultures. The capacity of cytokine production in relation to the number of mononuclear cells is higher in WB, or in PBMC having the same mononuclear cell concentration as WB, than in conventional cultures of concentrated PBMC (10(6)/ml). Because it mimics the natural environment, diluted WB culture may be the most appropriate milieu in which to study cytokine production in vitro.
Adult↗
Prevalence of dust mites in the homes of people with asthma living in eight different geographic areas of the United States.
The density and species prevalence of dust mites were determined at various times over a 5-year-period in 252 homes of dust mite sensitive people with asthma who lived in eight geographic areas of the United States (Cincinnati, Ohio; New Orleans, La.; Memphis, Tenn.; Galveston, Texas; Greenville, N.C.; Delray Beach, Fla.; San Diego and Los Angeles, Calif.). The most common dust mites found in the homes were Dermatophagoides farinae (DF), D. pteronyssinus (DP), Euroglyphus maynei (EM), and Blomia tropicalis. All homes in all locations contained Dermatophagoides spp. mites, but few homes were populated exclusively by either DF or DP alone. Most homes (81.7%) were coinhabitated by both DF and DP. In coinhabited homes one species was predominant and usually made up at least 75% of the total mite population. Prevalence of the dominant or only species present varied between homes within a geographic area. EM occurred in significant numbers in 35.7% of homes in New Orleans, Memphis, Galveston, Delray Beach, and San Diego. Blomia tropicalis occurred in these same cities but in low densities. For all dust samples, only 13 homes of the 252 sampled had 100 or fewer mites/gm dust, which is considered to be the threshold for sensitivity. Most homes had average mite densities of 500 or more mites/gm dust. The results of the present study suggest a significant and widespread occurrence of both DF and DP. Therefore extracts of both mite species should be considered for diagnostic tests and immunotherapy. Significant levels of EM were present in some areas. Thus sensitivity to EM should be considered in these areas.
Adolescent↗
Otitis media, language development, and parental verbal stimulation.
Examined the impact of recurrent otitis media in the first 3 years of life on verbal abilities of 3- to 4-year-old children and the potential for parental verbal stimulation to buffer the negative effects of intermittent hearing loss. Fathers and mothers of 56 children with variable histories of otitis media participated in videotaped parent-child interactions that were used to code level of parental verbal stimulation. Measures of the children's verbal abilities were the McCarthy Verbal Scale Index and a score for the child's verbalizations with each parent. Active and engaging parental verbalizations appeared to buffer the child's developing verbal abilities from the deleterious effects of recurrent otitis. Post hoc analyses examined the implications of task structure and parent sex on parent verbal stimulation. Discussion addresses the importance of paternal involvement for the home language environment and implications for intervention.
Age Factors↗
Adoptive immunotherapy with activated macrophages grown in vitro from blood monocytes in cancer patients: a pilot study.
Ninety-three collections of leucocytes by cytapheresis followed by separation of monocytes by centrifugal elutriation were undertaken in twelve metastatic cancer patients (four melanomas, six colon carcinomas, one ovarian carcinoma, and one lung cancer). The leucaphereses were performed aiming to collect a product, ready for introduction into the elutriation chamber, i.e., with low contamination by erythrocytes and granulocytes. The median collection of leucocytes was 7.3 x 10(9). After elutriation, purified monocytes (mean: 0.91 x 10(9)) were cultured with 3-5% autologous serum for 7 days in the presence of 250 IU/ml of recombinant human gamma-interferon (Rh-IFN gamma) for the last 18 h of culture. The median number of activated macrophages (MAK) available for reinfusion was 2.4 x 10(8) for each culture. The phenotypes and the antitumoral potentiality of MAK cells were documented. Reinfusions performed i.v. or i.p. were well tolerated with no major side effects. No complete tumor response was obtained. One partial response and two stabilizations of the disease were observed in one melanoma and two colon carcinomas.
Animals↗
Interleukin-2 in association with increasing doses of interferon-gamma in patients with advanced cancer.
Twenty-seven patients with evaluable metastatic cancer were treated with recombinant interleukin-2 (rIL-2) and escalating doses of interferon gamma (IFN-gamma). rIL-2 was infused over a 15 min period at a constant dose (8 x 10(6) IU/m2/8 h x 5 days first cycle, and 8 x 10(6) IU/m2/12 h x 5 days second and third cycles, with 9 days rest between each cycle). IFN-gamma was started 4 days before each cycle of rIL-2 and was given every other day at a dosage of 1 x 10(6) U/m2 x 3/cycle (four patients), 5 x 10(6) U/m2 x 3/cycle (four patients), 5 x 10(6) U/m2 x 5/cycle (four patients) and 10 x 10(6) U/m2 x 5/cycle (15 patients). Common side effects were fluid retention and hepatic toxicity (27 and 15% grade greater than or equal to 2); one ischemic chest pains and one acute respiratory distress occurred. Toxicities were not greater than those described with high dose rIL-2 alone and were similar in each dose level of IFN-gamma. No patient died from the procedure. Four patients responded, one complete response and three partial responses; all were treated with 25 or 50 x 10(6) U/m2/cycle of IFN-gamma (melanoma, two patients; renal cell carcinoma, one patient; lymphoma, one patient). Further phase II studies at these dosages are justified to precisely define the antitumoral efficacy of this association.
Adolescent↗
Adrenal function in adult asthmatics during long-term daily treatment with 800, 1,200, and 1,600 micrograms triamcinolone acetonide. Multicenter study.
A study to assess the effect of the long-term use of triamcinolone acetonide (TA) on adrenal function was conducted with 143 male and female patients with asthma who were randomly assigned to receive 800, 1200, or 1,600 micrograms of TA daily for six months. Adrenal function was assessed prior to treatment and after two weeks and one, three, and six months of TA use. The effect of TA was evaluated by measuring plasma cortisol levels just prior to and 30 min after a bolus IV injection of 0.25 mg cosyntropin. Adrenal suppression was assumed if the plasma concentration of cortisol did not increase by at least 7 micrograms/dl from the prestimulation value, and remained below 18 micrograms/dl 30 min after the cosyntropin injection. Urine collected for 24 h prior to each cosyntropin stimulation was assayed for free cortisol and related metabolites to confirm suppression. Although all treatment regimens caused some reduction in the 24-h excretion of corticosteroid products, none of the mean values was below the normal ranges. The mean data indicate that TA had no significant effect on adrenal function at any dose or at any time for the patients overall. Individually, three patients exhibited some reduction in adrenal function.
17-Hydroxycorticosteroids↗
Sphingofungins A, B, C, and D; a new family of antifungal agents. I. Fermentation, isolation, and biological activity.
In screening for antifungal inhibitors from fungi, four related antifungal agents have been isolated from the cultivation of Aspergillus fumigatus ATCC 20857. These agents were initially produced by the microorganism growing on a solid millet-based medium. A liquid medium containing both glucose and glycerol has also been developed in which these antibiotics are produced in two phases. These novel compounds, sphingofungins A, B, C, and D, show a limited spectrum of antifungal activity but were especially effective against Cryptococcus species.
Amino Acids↗
Incentive learning following reinforcer devaluation is not conditional upon the motivational state during re-exposure.
Three experiments analysed the effect of re-exposure to the reinforcer following aversion conditioning on instrumental performance. In the first experiment, groups of hungry and thirsty rats were trained to press a lever for sucrose, which was then followed by a single injection of lithium chloride (LiCl). On the following day, half the animals in each motivational condition received re-exposure to the sucrose solution; the remaining animals were not re-exposed. In a subsequent extinction test animals that had received re-exposure to the sucrose pressed less than animals that were not re-exposed. Moreover, the effect of re-exposure to the sucrose solution was similar following training under hunger and thirst. In the remaining studies, animals were trained to lever-press for sucrose while either hungry or thirsty. They were then injected with LiCl and re-exposed to the sucrose while either hungry or thirsty, i.e. in the same or different motivational state employed during training, or they were not re-exposed. Lever pressing was then tested in extinction in the training motivational state. As in the first experiment, re-exposure to the reinforcer after aversion conditioning enhanced the magnitude of the reinforcer devaluation effect. More importantly, re-exposure to the sucrose produced a comparable effect on instrumental performance, whether re-exposure was given under the same or different motivational state to that employed during training. These results suggest that the instrumental reinforcer devaluation effect depends upon a process of incentive learning, but that this process is not conditional upon the current motivational state of the animal.
Animals↗
Shift from posttranscriptional to predominant transcriptional control of the expression of the GM-CSF gene during activation of human Jurkat cells.
The expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene is differentially regulated in various cell types. We investigated the mechanisms controlling its expression in 12-O-tetradecanoylphorbol-13-acetate plus phytohemagglutinin-stimulated Jurkat cells, a human T-cell line. In unstimulated cells, GM-CSF mRNA was undetectable by Northern blot. Upon activation, it was detected from 3 h onward, with a progressive increase in the levels of the transcript up to 24 h of stimulation. Whereas cycloheximide treatment at the time of stimulation blocked mRNA induction, its addition at later times resulted in a marked increase in transcript levels. Run-on analysis showed that transcription of the GM-CSF gene was low to undetectable in unstimulated cells; stimulation led to transcriptional activation, which was weak at 6 h but had increased 16-fold at 24 h. In addition, the mRNA half-life decreased during activation, from 2.5 h at 6 h down to 45 min at 24 h. Cycloheximide treatment increased GM-CSF mRNA half-life (3- and 4-fold, respectively). Our results show: (a) both transcriptional and posttranscriptional signals regulate GM-CSF mRNA levels in activated Jurkat cells, (b) de novo protein synthesis is required for mRNA induction, whereas destabilizing labile proteins control the transcript stability, and (c) a shift from a posttranscriptional to a predominant transcriptional control of GM-CSF gene expression occurs during activation.
Cell Line↗
High-dose recombinant interleukin-2 and acute myeloid leukemias in relapse.
Interleukin-2 (IL-2) is able to induce the regression of metastatic cancers when administered in vivo. IL-2-activated natural killer cells and lymphocytes show, in vitro, activities against leukemic cells. To assess if in vitro observations could have significant clinical relevance, we evaluated the in vivo activity of high-dose recombinant IL-2 (6 to 8 x 10(6) IU/m2/8H intravenous bolus for 5 days) in 10 patients with acute myeloid leukemias (AML) in relapse after chemotherapy (n = 7) or autologous bone marrow transplantation (n = 3). Two patients achieved a complete remission and one had a minimal improvement in his marrow blast cells. Response was observed after one cycle of IL-2 in the two patients achieving a complete remission. These two patients relapsed at 3 and 4 months. These results showing clinical activity of high-dose recombinant IL-2 in AML invite further evaluation of this new form of immunotherapy in other clinical situations, like an adjuvant setting for selected groups of high-risk patients.
Adolescent↗
[Buserelin therapy in postmenopausal patients with advanced breast carcinoma].
Twenty-seven postmenopausal women with advanced breast cancer were treated with the potent LHRH-agonist buserelin. The drug was given s.c. three times daily at a daily dosage of 3 mg the first week and subsequently of 2 mg daily. Although pituitary gonadotropins were suppressed in all cases, no response was observed in 26 evaluable patients. This study does not confirm earlier findings suggesting a role for LHRH-agonists in the treatment of postmenopausal patients with breast cancer.
Adrenal Cortex Hormones↗
Reduction of graft failure by a monoclonal antibody (anti-LFA-1 CD11a) after HLA nonidentical bone marrow transplantation in children with immunodeficiencies, osteopetrosis, and Fanconi's anemia: a European Group for Immunodeficiency/European Group for Bone Marrow Transplantation report.
Forty-six infants and children suffering from either inherited immunodeficiency disorders (Wiskott-Aldrich syndrome, functional T-cell immunodeficiency with or without HLA class II expression deficiency), malignant osteopetrosis, or Fanconi's anemia received HLA-nonidentical bone marrow transplantation (BMT) from related donors. Bone marrow was T-cell depleted to reduce the risk of graft-versus-host disease (GVHD). To prevent graft failure, a mouse monoclonal antibody specific for the CD11a-lymphocyte function-associated antigen 1 (LFA-1) molecule was infused into the patients. Eleven patients received five infusions of 0.1 mg/kg every other day from day -3 to +5. Thirty-five patients received 0.2 mg/kg daily from day -3 to +6. The overall sustained engraftment rate was 72% instead of 26.1% in a historical control group of 24 patients similarly treated except for the infusion of the anti-LFA-1 antibody. No late rejection occurred. The T-cell depletion method (E-rosetting or Campath IM plus complement) resulted in different rate of engraftment (83.3% v 57.9%, respectively, P = .05). Engraftment rate was slightly but not significantly influenced by the degree of HLA incompatibility between donor and recipient. Acute GVHD of grade II or more occurred in 35.5% of the patients and the rate of chronic GVHD was 12.9%. The overall actuarial survival rate with a functional graft is 47.3% with a mean follow-up of 28.0 months for patients with immunodeficiency and osteopetrosis, while none of the four patients with Fanconi's anemia survived. The development of full T-cell functions took on the average 6 months and of full B-cell functions 10 months. Significant infectious problems developed in the majority of the patients during the posttransplant course. Epstein-Barr virus-induced B-cell proliferative syndromes were observed in seven patients, six of whom had Wiskott-Aldrich syndrome. Correction of immunodeficiency was comparable in terms of kinetics and quality with that observed in patients with severe combined immunodeficiency undergoing HLA-nonidentical BMT. Correction of osteopetrosis appears not to be different from what has been observed after HLA-identical BMT. The in vivo use of an anti-CD11a-LFA-1 antibody as an additional immunosuppressive therapy in HLA-nonidentical BMT may thus promote engraftment and survival with correction of the primary disease in a significant number of patients with life-threatening immunodeficiency and osteopetrosis, but not with Fanconi's anemia.
Antibodies, Monoclonal↗