Immunologic monitoring during combined radiochemoimmunotherapy in inoperable lung cancer

49 patients with advanced lung cancer underwent a combined treatment including radiochemoimmunotherapy. Before and at the end of the combined treatment, the immune status of the patients has been evaluated by testing the immunoreactivity to PPD in vivo and the phytohemagglutinin lymphocyte response and the rosette-forming cells in vitro. While the in vitro tests were not significantly modified by immunostimulation, as regards the immunoreactivity to PPD, we observed a positive conversion at the end of the treatment in 11 out of 25 patients who showed a negative reaction before therapy. All the patients who converted from negative to positive showed also a good response to therapy with regression or no progression of the tumor. Survival curves confirmed the prognostic value of PPD reactivity.     

Immunologic characterization of tumor markers in human ovarian cancer cell lines

OBJECTIVE: The purpose of this study was to evaluate the expression of a novel autologous ovarian tumor-associated antigen in eight human ovarian tumor cell lines compared with other ovarian tumor markers and products of oncogenes. METHODS: Autologous antibodies were eluted from human ovarian tumor-membrane fragments purified in our laboratory. These antibodies react with autologous ovarian tumor-associated antigens (AOTA) and have a high degree of specificity for human ovarian tumors. They do not bind to normal ovarian or nonovarian tissues, or to nonovarian neoplastic tissues. We evaluated eight human ovarian adenocarcinoma cell lines (2008, 2774, Caov-3, OVCAR-3, PA-1, SW 626, UCI 101, and UCI 107) by indirect immunofluorescence to determine the expression of AOTA relative to the ovarian cancer tumor marker CA 125 and the products of selected oncogenes (p 53, c-neu, and c-myc). RESULTS: The patterns and intensities of immunofluorescence correlated most closely between AOTA and c-neu. For example, AOTA and c-neu were detected in all eight cell lines and displayed very strong cytoplasmic fluorescence on cell lines 2774, UCI 101, and UCI 107. CA 125 was present in the cytoplasm of four of eight cell lines. A tumor suppressor gene product, p53, exhibited a nuclear staining pattern in six of eight cell lines. CONCLUSIONS: These data suggest that AOTA and the products of the c-neu oncogene may share certain epitopes. Current studies are underway to increase our understanding of the humoral response to ovarian cancer and the possible relationship to the expression of tumor oncogene products. Further characterization of AOTA will be necessary before early diagnostic tests can be developed.     

Immunologic tests in rheumatology

LEARNING OBJECTIVES: Reading this article will familiarize the reader with the application and interpretation of different autoantibody tests used in rheumatology. DATA SOURCES: Recent rheumatologic textbooks, relevant review articles, and seminal articles in English regarding specific tests. RESULTS: An understanding of this review should enable the reader to approach diagnostic testing systematically in a patient with a suspected connective tissue disease. CONCLUSIONS: The proper use and interpretation of appropriate immunologic tests are important in the diagnosis and treatment of patients with connective tissue diseases.     

Immunologic monitoring in lung allograft recipients

To identify patients with increased risk of chronic lung allograft rejection, we assessed the utility of an in vitro biopsy-derived lymphocyte growth assay and serum anti-HLA antibody screening as a complement to currently available methods of monitoring lung allograft recipients. Lymphocyte growth assay was performed on bronchoscopic fragments of tissue cultured in medium with rIL-2. Seventy-nine biopsies from 31 lung transplant recipients were tested by lymphocyte growth assay, and results were correlated with histopathology findings. Positive lymphocyte growth was found in 12/26 (46%) episodes of acute rejection, 5/44 biopsies without rejection (11%), and 0/9 episodes of bronchitis. Positive lymphocyte growth was seen in 7/16 (44%) grade A1 rejections and in 5/10 (50%) grade A2 rejections, as opposed to only 5/44 (11%) grade A0 (no rejection) biopsies (P < 0.01 for both A1 and A2 with respect to A0). Actuarial probability of remaining free from obliterative bronchiolitis (OB)* tended to be higher in patients who did not exhibit lymphocyte growth in biopsies. Sequential samples of sera obtained at the time of the biopsy were screened for lymphocytotoxic anti-HLA antibodies. Twenty-two of 44 recipients (50%) developed anti-HLA antibodies during the first postoperative year, exhibiting greater than 10% reactivity to an HLA reference panel of lymphocytes in four or more consecutive serum samples. Actuarial survival of lung allograft recipients with anti-HLA antibodies (n = 22) was lower than in those without anti-HLA antibodies (n = 22; P = 0.03). Of the 22 antibody producers, 7/12 died as a consequence of OB. Of the 22 non-antibody-producers, 1/2 deaths occurred as a consequence of OB. Anti-HLA antibodies were present in 9/11 instances of OB (82% sensitivity) and in 13/33 patients without OB (61% specificity; P = 0.03). These data indicate that lung transplant recipients with positive lymphocyte growth and anti-HLA antibodies are at an increased risk of chronic allograft rejection.     

Immunologic mechanisms in common rheumatologic diseases

Rheumatoid arthritis and seronegative spondyloarthropathies are rheumatologic diseases that likely are caused by inflammatory reactions occurring in genetically predisposed individuals mounting an immune response to the antigen. Understanding the immunopathology of these diseases provides insight into their etiology, pathogenesis, and a rationale for therapies targeting immune component interactions. Although the antigen in rheumatoid arthritis is not known, several bacterial antigens have been associated with seronegative spondyloarthropathies. These antigens result in an interaction between the human leukocyte antigen-B27 restricted CD8 positive T lymphocytes and the antigen presenting cell, producing an inflammatory response. Rheumatoid factors are autoantibodies directed against the fragment crystallizable portion of the immunoglobulin G. Rheumatoid factor immunoglobulin G immune complexes contribute to the inflammatory events in the rheumatoid joint, and may play an important role in antigen presentation. A novel antigen capture enzyme linked immunosorbent assay was developed that mimicked B cell surface expressed rheumatoid factor. Conversely, a direct binding enzyme linked immunosorbent assay mimicked secreted rheumatoid factor. Comparison of rheumatoid binding enzyme linked immunosorbent assays showed that the physical state of rheumatoid factor can affect binding characteristics. The state of glycosylation of immunoglobulin G may contribute to its antigenic structure. These physical characteristics may be important in rheumatoid factor's pathogenic role in rheumatoid arthritis.     

Neurophysiological evaluation of sexual dysfunction in patients operated for colorectal cancer

Severe dieting and negative energy balance usually lead to the occurrence of amenorrhea together with several endocrine disturbances such as the "low T3 syndrome" and an abnormal GH secretion. To evaluate whether estrogen replacement therapy (ERT) affects thyroid hormones and GH secretion, two groups of patients affected by weight-loss-related amenorrhea and with low plasma T3 levels were treated with two different schedules of ERT using 50 or 100 micrograms estradiol transdermal patches twice a week (Dermestril, Rottapharm, Monza, Italy). Before and after 5 weeks of therapy in each patient thyroid hormones, spontaneous GH secretion and GH-RH-induced GH release were evaluated. After ERT, plasma GH and IGF-1 levels increased in both groups and a consistent change in GH spontaneous release was observed. Conversely the low T3 plasma levels and GH-RH-induced GH response were not modified by ERT. Our present data suggest that in amenorrhea related to weight-loss, hormonal abnormalities are only in part dependent from the hypoestrogenic condition.     

Immunologic function and survival in hemodialysis patients

Human immunodeficiency virus type 1 integrase (HIV-1 IN) which catalyzes viral DNA integration into the host genome of infected cells represents an attractive target for AIDS therapy. We have previously demonstrated the ability of the IN-(147-175)-peptide derived from the catalytic core domain of HIV-1 IN to inhibit the enzyme activity in vitro. IN-(147-175)-peptide contains four heptad repeats and displays a high propensity for coiled-coil formation while its [P159]IN-(147-175)-peptide analog (Lys159-->Pro in the protein, Lys13-->Pro in the peptide) is unable to form a stable coiled-coil and is devoid of inhibitory activity [Sourgen, F., Maroun, R. G., Frère, V., Bouziane, M., Auclair, C., Troalen, F. & Fermandjian, S. (1996) Eur. J. Biochem. 240, 765-773]. Now, we report results from an NMR study on IN-(147-175)-peptide and [P159]IN-(147- 175)-peptide as well as on an optimized [E156, A163, A167]IN-(147-175)-peptide that is a better inhibitor of IN than IN-(147-175)-peptide. While in aqueous solution, IN-(147-175)-peptide and [P159]IN-(147-175)-peptide display only nascent helical features, [E156, A163, A167]IN-(147-175)-peptide exhibits 20% of helical content. In 20% trifluoroethanol/80% H2O, the helix content is the highest for [E156, A163, A167]IN-(147-175)-peptide (approximately 70%) and the lowest for [P159]IN-(147-175)-peptide (approximately 40%), due to a local helix break caused by the Pro residue. The NHs of residues in the two central helical heptads (a-g) of IN-(147-175)-peptide and [E156, A163, A167]IN-(147-175)-peptide display a regular periodic variation of their temperature coefficients in 20% trifluoroethanol. The b, c and f residues on the hydrophilic face of the amphipathic helix show high coefficients reflecting hydrogen bonded NHs, while the a and d residues on the hydrophobic face exhibit low coefficients, near random-coil values. The particular arrangement of the hydrophobic side-chains of a and d residues at the coiled-coil interface reduces the access of trifluoroethanol molecules to their amide groups. The inability of trifluoroethanol molecules to create interactions with the amide C=O groups, these being required to strengthen the intrahelical C=O...H-N hydrogen bonds, is the main cause for observation of heptadic a and d residues with low NH temperature coefficients. Such effects concern mostly the two central helical heptads of IN-(147-175)-peptide and [E156, A163, A167]IN-(147-175)-peptide implying that these ones are engaged in stable parallel coiled coils. Our results provide a link between the propensity of peptides for helix formation, their coiled-coil properties and their efficiency to inhibit IN.     

Immunologic protection afforded by sunscreens in vitro

Several studies have suggested a lack of correlation between sunscreen sun protection factor and protection of the skin immune system, potentially allowing greater damage to the skin by removing the natural protective erythemal response to sun exposure. Despite this, routine testing of immune protection afforded by sunscreens is not performed by industry. Current laboratory methods for investigating the efficacy of sunscreen protection of epidermal immune function use the induction of contact hypersensitivity or epidermal cell alloantigen presentation. Animal models, cell culture systems, and in vivo human studies are commonly employed, but all these systems have significant drawbacks for use in routine testing. The purpose of this study was to develop an in vitro system for testing the immunologic protection afforded by sunscreens in human skin. Five test sunscreens plus a vehicle control were tested in a "blind" fashion for their in vitro level of immune protection. Creams were applied in a standard manner to human whole skin explants and were irradiated over a range of physiologic doses using an Oriel solar simulator. A mixed epidermal lymphocyte reaction was used to quantify epidermal alloantigen-presenting capacity, in the presence or absence of test cream, for five explants. Results consistently demonstrated that all the test sunscreens protected beyond their designated sun protection factors, whereas the vehicle conferred no protection. The explant-mixed epidermal lymphocyte reaction system gave consistent, reproducible results and may prove useful for the allocation of an immune protection factor to all sunscreens.     

Immunologic aspects of renal disease

The kidney can become involved in immune-mediated diseases through 3 mechanisms. It can be the primary target of antibody-mediated injury. Good-pasture syndrome, with antibodies directed at the glomerular basement membrane, is an example of this type. The kidney can be injured by immune complexes that are trapped in the kidney and cause local inflammation. Examples include systemic lupus erythematosus and IgA nephropathies. Finally, the kidney can be injured by immune responses initiated in other organs. In Wegener granulomatosis, inflammation begins in the airway but results in glomerulonephritis. Currently available therapies lack efficacy and specificity. New therapies based on pathophysiology are being developed in animal models.     

Immunologic function of the harderian gland in chickens

1. The pharmacokinetics of methyldopa after oral and intravenous administration was studied in hypertensive and normotensive patients. After intravenous administration methyldopa plasma concentrations decayed according to a two-compartment open model. 2. For intravenous administration the overall elimination constant Ke1 was 0.56 +/- 0.03 h-1, the volume of distribution of the central compartment 0.29 +/- 0.80 1 kg-1 and the plasma clearance rate 11.2 +/- 0.6 1 h-1. 3. Plasma half-times during the beta-phase of the methyldopa plasma decay curve following intravenous and oral administration were 2.8 +/- 1.3 and 2.1 +/- 0.7 h, respectively. 4. Maximal plasma levels in hypertensive out-patients show great variation and range from 0 to 1.9 microgram ml-1. 5. No relationships were found between maximal methyldopa plasma levels in patients under treatment and control of hypertension.     

Immunologic monitoring and aspergillosis in renal transplant patients

Three cases of pulmonary aspergillosis in a "high risk" population of renal transplant recipients are presented. The source of infection was traced to the forced air exhaust system of the Transplantation Unit. Early definitive diagnosis of the infection was very important for effective management. Immunologic monitoring was demonstrated to be instrumental in indicating the early presence of infection, and as a guideline to reduced immunosuppression during therapy. Bronchoscopy with brushings and endobronchial cavitary biopsy were valuable methods for obtaining the infected tissue. Amphotericin B was effective when therapy was started early. Adequate levels of the drug were obtained by varying the dose and frequency of administration according to serum inhibitory titers. Control of infection was aided by immunologic monitoring at regular intervals.     

Immunologic studies in a case of baker's asthma

A 28-year-old baker with 13 years of occupational experience has developed, over the past several years, sinusitis, rhinitis, contact dermatitis, and asthma. Clinically, all of his symptoms were felt to be related to occupational exposure. Immunologic evaluation consisted of the following tests: intradermal skin testing, leukocyte histamine release, total serum IgE, PK transfer with immunoadsorption, and specific antigen bronchial challenge. Analysis of results would tend to implicate a type I, IgE-mediated immunologic reaction.     

Technetium-99m dimercaptosuccinic acid and ifosfamide tubular dysfunction in children with cancer

Quantitative 99mTc-dimercaptosuccinic acid (99mTc-DMSA) renal scintigraphy was used to asses ifosfamide-induced changes in renal function in 11 children who received chemotherapy for various malignancies. Serial measurements of absolute 99mTc-DMSA renal uptake, calculated on conjugated views, were performed during and after chemotherapy. Data of 37 studies obtained before and at different cumulative dose levels of ifosfamide were analysed in relation to clinical and biochemical parameters. A highly significant relationship between 99mTc-DMSA uptake and cumulative ifosfamide dose was found (P < 0.001). The most frequently observed abnormal pattern on scintigraphic images was decreased kidney uptake together with increased accumulation in bladder. 99mTc-DMSA uptake was more consistent than beta 2-microglobulin values in urine and more sensitive than quantitative hyperaminoaciduria and tubular resorption of phosphate for the detection of ifosfamide-induced tubular dysfunction. 99mTc-DMSA uptake was decreased in both patients with and patients without clinical toxicity. Persistently reduced 99mTc-DMSA uptake was observed in four patients during follow-up; in one of them, who was asymptomatic after ifosfamide therapy, sudden onset of Fanconi syndrome was observed when he was retreated with carboplatin 1 year later. It is concluded that 99mTc-DMSA renal scintigraphy is a suitable method to assess progressive ifosfamide-induced tubular injury whereas scintigraphic imaging is helpful for interpreting renal uptake changes. The test is able to detect subclinical injury and may potentially predict high risk at retreatment.