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PubMed2005

The economics of drug abuse: a quantitative assessment of drug demand.

Behavioral economic concepts have proven useful for an overall understanding of the regulation of behavior by environmental commodities and complements a pharmacological perspective on drug abuse in several ways. First, a quantitative assessment of drug demand, equated in terms of drug potency, allows meaningful comparisons to be made among drug reinforcers within and across pharmacological classes. Second, behavioral economics provides a conceptual framework for understanding key factors, both pharmacological and environmental, that contribute to reductions in consumption of illicit drugs. Finally, behavioral economics provides a basis for generalization from laboratory and clinical studies to the development of novel behavioral and pharmacological therapies.

Animals↗
PubMed2002

Development of a yeast assay for rapid screening of inhibitors of human-derived Pneumocystis carinii dihydrofolate reductase.

Human-derived Pneumocystis carinii dihydrofolate reductase (DHFR) was expressed in a Saccharomyces cerevisiae strain whose growth depends on complementation by this enzyme. We utilized a quantitative assay to measure the sensitivity of this yeast strain to DHFR inhibitors. This assay should be useful for identifying new inhibitors of human-derived P. carinii DHFR.

Animals↗
PubMed1981

Characterization of hemadsorption-negative mutants of Mycoplasma pneumoniae.

Previously isolated mutants of Mycoplasma pneumoniae incapable of hemadsorption were characterized with respect to specific protein content, tracheal ring attachment capability, and virulence for both in vitro and in vivo model systems. Two-dimensional gel electrophoresis revealed both quantitative and qualitative differences between the protein complements of two different mutant strains and that of the virulent parent strain. Studies of mycoplasma attachment to hamster tracheal rings in vitro demonstrated that only one of these mutant strains still possessed the ability to attach to the respiratory epithelium via neuraminidase-sensitive receptors. Measurement of [3H]orotic acid uptake in mycoplasma-infected tracheal rings indicated that infection with the hemadsorption-negative mutants resulted in only slight reductions of ribonucleic acid synthesis, similar to levels observed for tracheal rings infected with an avirulent strain of M. pneumoniae. The virulence potential of the two mutant strains was further investigated by utilizing the hamster model system. Both mutant strains were rapidly cleared from the lungs of infected animals and produced little or no microscopic pneumonia.

Animals↗
PubMed2003

Silent nephritis in systemic lupus erythematosus.

Silent lupus nephritis (SLN) was investigated in 42 renal asymptomatic patients and compared with 49 untreated patients with overt lupus nephropathy (OLN). Urinary sediment, quantitative proteinuria, creatinine clearance, antinuclear antibodies (ANA), complement, circulating immune complexes (CIC) and renal biopsies were evaluated in all of the patients. Forty-one out of the 42 (97.6%) patients had SLN according to histopathological findings. Results showed that the mean age, female/male ratio and the clinical activity index (SLEDAI) were similar in both groups (P > 0.05). The prevalence of ANA, anti-ds DNA, anti-ENA autoantibodies and C4 serum levels showed no statistical differences between the two groups (P > 0.05). Conversely, in the OLN group, elevated CIC and diminished CH50 and C3 serum levels were significantly different (P < 0.01). WHO class II was the predominant renal lesion in the group with SLN (P < 0.0001), whereas class IV was in the OLN patients (P < 0.0001). We conclude that, in our series, SLN was highly prevalent in renal asymptomatic patients with otherwise systemic lupus erythematosus. Furthermore, abnormal levels of CIC, CH50 and C3 associated with WHO class II suggest a moderate but ongoing activation of immune-mediated renal injury mechanisms.

Adolescent↗
PubMed1986

IgG subclass deficiency in children with IgA deficiency presenting with recurrent or severe respiratory infections.

A group of 22 children presenting with recurrent or severe respiratory tract infections who had low IgA levels (more than 2 SD below the mean for age) were examined for IgG subclass deficiency. Patients were screened for possible defects in neutrophil chemotaxis, bactericidal, fungicidal, and quantitative iodination activity, as well as for complement function. The majority of the patients showed IgG subclass levels below the mean for age. Nine of the children showed definite IgG subclass deficiency and at least two showed definite deficiency of more than one IgG subclass. The predominant subclass deficiency was found to be IgG1. While nine children showed IgG4 levels below the level detectable by the technique used, it is not possible to assess whether these patients are deficient in this isotype since some healthy subjects also give values below the level of detection. Most of the patients who had very low (1-6 mg/dl) or undetectable (less than 1 mg/dl) levels of serum IgA did not show IgG subclass deficiencies, while IgG subclass deficiencies were common among those with borderline low IgA levels (slightly more than 2 SD below the mean for age). Nine children showed total IgG levels close to 2 SD below mean for age, and at least six of these showed IgG subclass deficiency. The result suggests that patients with recurrent and/or severe respiratory infections who have borderline IgA and IgG levels may have IgG subclass deficiencies and if they do could benefit from immunoglobulin therapy.

Blood Bactericidal Activity↗
PubMed1998

Study of heteroserum-induced rat liver fibrosis model and its mechanism.

AIM:To investigate the morphological changes in the process of heteroserum induced rat liver fibrosis and the mechanism of fibrogenesis of this model.METHODS:A model of heteroserum-induced rat liver fibrosis was established by intraperitoneal injection of porcine serum. In addition to the observation of the morphological changes of this model, the infiltration of eosinophils and mast cells were measured quantitatively and the deposition of IgG and complement C(3) was detected by immunofluorescence.RESULTS:The rat liver fibrosis was induced successfully at the end of the 8th week after the injection of heteroserum.Besides the increase of hepatic stellate cells (HSC) during the process of liver fibrosis,proliferation and activation of primary mesenchyma cells (PMCs) were also found.In the early stage, the infiltration of eosinophils and mast cells was significantly increased and the deposition of IgG and complement C(3) was positive in the portal tracts and septa, while gradually reduced after the injection was stopped.CONCLUSION:This model is suitable for the research on liver fibrogenesis; the pathogenesis of this model may be related with the allergen-induced late phase reaction (LPR) caused by the injection of heteroserum, and the HSCs and the PMCs are important sources of ECM-producing cells.

Journal Article↗
PubMedDate not supplied

[Acute disseminated encephalomyelitis as initial clinical manifestation of common variable immunodeficiency. A case report].

Common variable immunodeficiency (CVID) is a primary immunodeficiency disease characterized by severe and recurrent infections which affect both lung and gastrointestinal systems. On the contrary, central nervous system involvement, related to virus infections, is an important, rare and usually fatal complication occurring in a later phase of the disease. Furthermore, CVID may predispose to a variety of autoimmune diseases. Here, we report the case of a 20 years old girl who developed acute disseminated encephalomyelitis as the first clinical feature in CVID. The infective agent was not determined and there was no history of recent vaccinations. CVID was diagnosed on the basis of the significant reduction of serum immunoglobulin concentration, in the absence of either diseases responsible for secondary immunodeficiency or functional and/or quantitative abnormalities of lymphocyte subsets, phagocytes and complement fractions. The treatment with high doses of native intravenous immunoglobulins (IVIG) combined with corticosteroids in the early phase led to a complete recovery with restitutio ad integrum. This case outlines the possible relationship between autoimmune diseases and infections in CVID, as suggested by the finding of either viral encephalitis in CVID patients and the well-known autoimmune pathogenesis of acute disseminated encephalomyelitis. In such a condition, the combination of IVIG and corticosteroids may offer considerable advantages in terms of therapeutical efficacy.

Adrenal Cortex Hormones↗
PubMed1977

[Application of CH50 assay to the detection of circulating immune complexes (author's transl)].

Detection and titration of circulating immune complexes appear as an essential tool for the diagnosis and prognostic evaluation of immune complex diseases. Authors propose a simple, rapid, senstive and quantitative method based on the evaluation of complement by soluble immune complexes measured by 50% hemolytic activity. This technique was compared to the I125 C1q binding test and may be recommended for clinical laboratory use.

Antigen-Antibody Complex↗
PubMed2005

[Proteomics and its role in medicine].

Proteomics is a new methodological and conceptual approach to the study of live systems, which aims to map the whole proteom - the protein complement of genome. It aspires to describe quantitatively and qualitatively all proteins present at the given moment in the cell, tissue or the organism. The principal tools of proteomics are separation techniques based on electrophoresis and chromatography, which are used to fractionate complex protein mixtures and namely the mass spectrometry used for the identification of individual proteins. Proteomics represents very young and rapid developing specialization, which has already proved its valuable potential for the study of various physiological and pathlogical molecular mechanisms and for the direct use in the diagnostics of serious diseases.

Chromatography↗
PubMedDate not supplied

Image cytometry DNA analysis of dysplastic squamous epithelial lesions in the larynx.

The Feulgen-DNA content of cell nuclei from the human larynx was assessed in 62 lesions from 14 patients with dysplastic and cancerous lesions and in 14 control patients with non-neoplastic chronic laryngitis. All the carcinomas displayed aneuploid cell nuclei, and the cellular DNA content was substantially altered in dysplasias which later progressed to cancer in situ or invasive cancer. Thus the process of laryngeal carcinogenesis can be monitored not only by histological changes, but also by cellular DNA aberrations. Quantitative DNA analysis appears to be a complement to the histopathological evaluation of laryngeal lesions in the search for neoplasia.

Biopsy↗
PubMed1978

Sequential studies of bovine leukemia virus antibody development in dairy cattle over a four-year period.

Serological examinations using the agar gel immunodiffusion and immunofluorescence tests were undertaken to study: a) the development of bovine leukemia virus infections in a given herd under field conditions monitored by antibody development, b) the reproducibility of the results of serological examination during 22 sequential tests, c) the antibody titre variations amongst individual animals. A total of 286 Friesian cattle representing 2,352 serum samples was tested at regular intervals over a period from 1974/75 to 1978. The percentage of animals with bovine leukemia virus antibodies continuously increased during the observation period from an initial 4.8% (1974/75), 9.7% (1976), 34.2% (1977) to 52.6% (1978). On the basis of 22 sequential tests representing 1,672 serum samples obtained from 76 animals no false positive reactions were seen in the immunodiffusion test. Thirty-six (14.2%) out of 254 animals, however, showed variations of the antibody titre leading to a shift from positive to negative or negative to positive results, respectively. AnothFr three cattle (1.2%) shifted from a positive to negative immunodiffusion result and maintained their negative reactivity for at least two following tests. But they still had specific antibodies if tested by the immunofluorescence test. A detailed analysis of the group of variable reactors supports the view that a more sensitive and quantitative test system may be helpful to complement the presently used immunodiffusion test for the eradication of enzootic bovine leukosis.

Animals↗
PubMed1987

Antigenic phenotype of NIH 3T3 cell line.

The antigenic phenotype of the NIH 3T3 cell line was examined by use of a panel of monoclonal antibodies and alloantisera specific for H-2 and several non-H-2 antigens. The binding of antibodies to cell surface antigens was examined by a complement-dependent microcytotoxicity test and indirect immunofluorescence quantitated by flow cytometry. The phenotype of the tested NIH 3T3 cell line was H-2q, Qa-2, Ly-6.2, Thy-1.2, Ly-23.2, and 9F 3+. The expression of H-2 antigens (Kq, Dq/Lq) was lower than that in the T-lymphocytes of the B10.Q (H-2q) strain, and the expression of Qa-2 was very low. From the Ly-6 complex, the antigen Ly-m6.2A was strongly expressed, while Ly-m.6B, Ly-m.6C, and antigens ThB and H9/25 were not detected. A monoclonal antibody specific for the nonpolymorphic antigen 9F 3 brightly stained 100% of NIH 3T3 cells. Inasmuch as the NIH 3T3 immortalized cell line was developed from outbred NIH Swiss mice, a syngeneic recipient for this cell line does not exist. However, on the basis of the determined antigenic phenotype the host most compatible to NIH 3T3 cells can be selected for in vivo experiments, where an immunocompetent recipient is required. Two inbred mouse strains identical with NIH 3T3 cells in the antigens examined in this study, B10.Q and DBA/1, are of potential use for transplantation with NIH 3T3 cells.

Animals↗
PubMed1978

Exacerbation of mixed connective tissue disease during Salmonella gastroenteritis--serial immunological findings.

A patient with mixed connective tissue disease is described who developed fever and polyserositis after the onset of Salmonella gastroenteritis. Antiribonucleoprotein antibodies, serum complement, and circulating immune complexes were studied quantitatively throughout the course of her illness. If the Salmonella infection were responsible for the exacerbation of mixed connective tissue disease, as the sequence of events suggests, the mechanism appeared to involve deposition of previously circulating immune complexes in affected tissues.

Adult↗
PubMed1980

Comparison of radial immunodiffusion and laser nephelometry for quantitating some serum proteins.

After quantitating immunoglobulins G, A, and M and complement C3c and C4 in serum by using a laser nephelometer coupled with a data processor, I compared these results with values obtained by an early-readout radial immunodiffusion method. Day-to-day precision was better for nephelometry than for radial immunodiffusion for all proteins analyzed. The average coefficient of variation was 6.0% for nephelometry and 9.9% for radial immunodiffusion. Comparison of these methods gave ranked correlation coefficients of 0.945, 0.981, 0.932, 0.803, and 0.792 for IgG, IgA, IgM, C3c, and C4, respectively. Nephelometry gave significantly higher values than radial immunodiffusion for IgG, IgA, IgM, and C3c, and significantly lower values for C4 (p less than 0.001). Part of this bias was found to be due to the equation programmed in the data processor for calculating the standard curves. Within 95% limits, nephelometry gave higher normal ranges than radial immunodiffusion for IgG, IgA, and IgM. Other possible factors that can produce this bias are discussed.

Adolescent↗
PubMed1981

Absence of common ALL antigen on normal bipotent myeloid, erythroid, and granulocyte progenitors.

The presence of the common acute lymphoblastic leukemia antigen (CALLA) on leukemic cells from the great majority of patients with non-T cell acute lymphoblastic leukemia and chronic myelogenous leukemia in blast crisis suggests that CALLA could be differentiation antigen expressed by normal lymphoid and myeloid stem cells. Treatment with a murine monoclonal anti-CALLA antibody and complement lysed CALLA-positive leukemic cells quantitatively, whereas similar treatment of nucleated cells from peripheral blood and bone marrow failed to affect the expression, in semisolid culture, of CFU-G/E, BFU-E, CFU-E, or CFU-C. These data suggest that CALLA is not a normal differentiation antigen of the myeloid bipotent cell or its committed progenitors.

Acute Disease↗
PubMed1994

Alpha 1-antitrypsin Pittsburgh (Met358-->Arg) inhibits the contact pathway of intrinsic coagulation and alters the release of human neutrophil elastase during simulated extracorporeal circulation.

Cardiopulmonary bypass prolongs bleeding time, increases postoperative blood loss, and triggers activation of plasma proteolytic enzyme systems and blood cells referred to as the "whole body inflammatory response". Contact of blood with synthetic surfaces leads to qualitative and quantitative alterations in platelets, neutrophils, contact and complement systems. Contact and complement pathway proteins both induce neutrophil activation. alpha 1-antitrypsin Pittsburgh (Met358-->Arg), a mutant of alpha 1-antitrypsin, is a potent inhibitor of plasma kallikrein and thrombin. We investigated whether this recombinant mutant protein inhibited platelet activation, as well as contact and/or complement-induced neutrophil activation during simulated extracorporeal circulation. Arg358 alpha 1-antitrypsin did not prevent the 34% drop in platelet count at 5 min of recirculation, did not block the 50% decrease in ADP-induced platelet aggregation at 120 min of recirculation, nor inhibit the release of 6.06 +/- 1.07 micrograms/ml beta-thromboglobulin at 120 min of recirculation suggesting that the inhibitor had little effect on platelet activation. However, Arg358 alpha 1-antitrypsin totally blocked kallikrein-C1-inhibitor complex formation but not C1-C1-inhibitor complex formation. Most importantly, Arg358 alpha 1-antitrypsin decreased the release of 1.11 +/- 0.16 micrograms/ml human neutrophil elastase by 43%. The attenuation of neutrophil activation in the absence of an effect on complement activation via the classical pathway, supports the concept that kallikrein is a major mediator of neutrophil degranulation during cardiopulmonary bypass.

Arginine↗
PubMed1993

[Acoustic evaluation and use of computers].

Thanks to the measurements of the acoustical parameters of voice and speech, an objective semeiology can be set up to assess a diagnosis and, to a certain extent, a prognosis and the follow up after therapy. A computerized analysis is a good complement to the clinical evaluation. It gives quantitative values, with statistics and the means to compare patients to themselves and to other patients. After defining the parameters we are interested in, we review the different softwares at our disposal with their limits.

Diagnosis, Computer-Assisted↗
PubMed1979

Assay for antibody mediated cytotoxicity of mouse spermatozoa by 86rubidium release.

The analysis of the antigenic structure of murine spermatozoa has been hampered by the lack of a convenient objective serological assay. Spermatozoa, in common with other cells, are capable of concentrating 86rubidium. Antibody mediated complement dependent cytotoxicity of murine spermatozoa has been quantitated by measuring release of 86rubidium from pre-labeled spermatozoa. We have used this assay to study the murine T/t locus.

Animals↗