Dinitrochlorobenzene Skin Test Research Articles

Ocimum sanctum Linn. Leaf Extracts Inhibit Acetylcholinesterase and Improve Cognition in Rats with Experimentally Induced Dementia

Cognitive disorders such as dementia, attention deficits, and Alzheimer's disease (AD) have been well investigated. However, effective interventions for the promotion and progression of AD are unavailable to date. The present work was undertaken to investigate the effects of the aqueous (300 and 500 mg/kg) and alcoholic (300 and 500 mg/kg) extracts of Ocimum sanctum Linn. leaves as an antidementic and anticholinesterase agent and also as an immunostimulant in rats. Maximal electroshock, atropine, and cyclosporine were used to induce dementia. The passive avoidance task was used for assessing memory. Acetylcholinesterase (AChE) activity was estimated in different parts of the brain, and immune status was studied using dinitrochlorobenzene (DNCB) skin sensitivity tests. In all the three models both aqueous and alcoholic O. sanctum extracts decreased the time taken to reach the shock-free zone and the number of mistakes and significantly decreased the AChE activity in rats. O. sanctum treatment significantly increased the induration in the DNCB skin test. Therefore, O. sanctum was shown to be useful for the management of experimentally induced cognitive dysfunctions in rats.

Autologous tumor-derived heat-shock protein peptide complex-96 (HSPPC-96) in patients with metastatic melanoma

BackgroundGlycoprotein-96, a non-polymorphic heat-shock protein, associates with intracellular peptides. Autologous tumor-derived heat shock protein-peptide complex 96 (HSPPC-96) can elicit potent tumor-specific T cell responses and protective immunity in animal models. We sought to investigate the feasibility, safety, and antitumor activity of HSPPC-96 vaccines prepared from tumor specimens of patients with metastatic melanoma.MethodsPatients with a Karnofsky Performance Status >70% and stage III or stage IV melanoma had to have a metastasis >3 cm in diameter resectable as part of routine clinical management. HSPPC-96 tumor-derived vaccines were prepared in one of three dose levels (2.5, 25, or 100 μg/dose) and administered as an intradermal injection weekly for 4 consecutive weeks. In vivo induction of immunity was evaluated using delayed-type hypersensitivity (DTH) to HSPPC-96, irradiated tumor, and dinitrochlorobenzene (DNCB). The γ-interferon (IFNγ) ELISPOT assay was used to measure induction of a peripheral blood mononuclear cell response against autologous tumor cells at baseline and at the beginning of weeks 3, 4, and 8.ResultsAmong 36 patients enrolled, 72% had stage IV melanoma and 83% had received prior systemic therapy. The smallest tumor specimen from which HSPPC-96 was prepared weighed 2 g. Twelve patients (including 9 with stage IV and indicator lesions) had a negative DNCB skin test result at baseline. All 36 patients were treated and evaluable for toxicity and response. There were no serious toxicities. There were no observed DTH responses to HSPPC-96 or to autologous tumor cells before or during treatment. The IFNγ-producing cell count rose modestly in 5 of 26 patients and returned to baseline by week 8, with no discernible association with HSPPC-96 dosing or clinical parameters. There were no objective responses among 16 patients with stage IV disease and indicator lesions. Among 20 patients treated in the adjuvant setting, 11 with stage IV melanoma at baseline had a progression-free and overall survival of 45% and 82%, respectively, with a median follow-up of 10 years.ConclusionTreatment with autologous tumor-derived HSPPC-96 was feasible and safe at all doses tested. Observed immunological effects and antitumor activity were modest, precluding selection of a biologically active dose. Nevertheless, the 25-μg dose level was shown to be practical for further study.

T-cell evaluation in patients with colon cancer: dinitrochlorobenzene skin testing versus plasma levels of sIL-2r and sCD8.

Developing reliable methods to test the T-cell system may be important in the treatment of colon cancer patients with 5-fluorouracil/levamisole. In a pilot study we explored whether DNCB (dinitrochlorobenzene) skin testing correlated with plasma levels of soluble interleukin-2 receptor (sIL-2r) and soluble CD8 (sCD8) and, secondly, whether the application of DNCB had any influence on the production of sIL-2r and sCD8. In 10 patients with advanced colon cancer and in 10 healthy volunteers, plasma levels of sIL-2r and sCD8 were measured before and 10 days after the application of 2 mg DNCB on the inner side of the forearm. As expected, colon cancer patients showed a depressed immune system compared to healthy volunteers (DNCB skin test: P = .005, sIL2r [medians 700 vs 295, P = .002], sCD8 [medians 158 vs 90, P = .03], M-W test). The plasma levels for sIL-2r and sCD8 were significantly lower in the skin-positive cases (P = .01 and P = .03, M-W test). However, a large overlap in plasma levels could be observed between the two skin categories. DNCB had no influence on the production of sIL-2r and sCD8; median change skin-negative and skin-positive -10 vs +25, P = .14, respectively; 48 vs 0, P = .32 (M-W test). DNCB skin testing and plasma levels of sIL-2r and sCD8 seem to be equally useful in evaluating the T-cell system and can be used simultaneously.

Delayed hypersensitivity and differences of histologic pattern in allergic cutaneous vasculitis.

Fourteen patients with allergic cutaneous vasculitis of either the polymorphonuclear (PMN)- or the mononuclear (MN)-predominant type were studied as regards the following parameters: the disease duration, histology, monoclonal antibody typing of the mononuclear cell infiltrate from recent lesions, and the delayed hypersensitivity (DH) response, assessed both by recall antigens (tuberculin type) and the dinitrochlorobenzene skin test. From the results, it was shown that in PMN-predominant vasculitis, DH reactions were well elicited, whereas in MN-predominant vasculitis, DH skin reactions were somehow impaired. In MN-predominant cases, many OKT3+, OKT4+, OKT8+, and OKM1+ cells were usually seen to surround the skin vessels, whereas in PMN-predominant cases, rare OKT8+, OKT4+, or OKM1+ cells were seen in the dermis. The epidermal dendritic cell system, as revealed by the Na(1)34 monoclonal antibody, was unaffected in both types of allergic cutaneous vasculitis.

Impaired cell mediated immunity in haemophilia in the absence of infection with human immunodeficiency virus.

The cell mediated immune response was evaluated in vivo in 29 patients with clinically severe haemophilia by means of the dinitrochlorobenzene skin test. All patients had a response below the median normal value, and in 19 the response was on or below the lower limit of the normal range. There was no difference in skin response between patients positive and negative for the human immunodeficiency virus (HIV; formerly known as human T cell lymphotropic virus III or lymphadenopathy associated virus). In the whole group, and in seronegative patients (n = 17), there was an inverse relation between exposure to clotting factor and skin response. In seropositive patients (n = 12) no such association was apparent. This study shows that clotting factor concentrate impairs the cell mediated immune response to a new antigen in the absence of infection with HIV.

Prediction of the occurrence of Marek’s disease in chickens on the basis of the quantitation of cell-mediated immunity

Cell mediated immunity was assayed in chickens on the basis of the dinitrochlorobenzene skin test, T lymphocyte numbers in peripheral blood and the graft-versus-host reaction. It was found that chickens that were to develop clinical Marek's disease following exposure to Marek's disease virus had significantly lower prechallenge levels of cell mediated immunity than those that were resistant to Marek's disease. The graft-versus-host reaction had a smaller coefficient of variation than the other two tests, and it was concluded that this test is likely to be the most reliable indicator of the outcome of infection with Marek's disease virus.

The Predictive Value of 2,-4, Dinitrochlorobenzene Skin Testing in Patients with Bilharzial Bladder Cancer

A group of 40 patients with bilharzial bladder cancer underwent quantitative skin testing with dinitrochlorobenzene and purified protein derivative of tuberculin before radical surgery. Correlations were made between various clinical parameters, patient outcome, skin test results and pathologic changes in the resected bladder and draining lymph nodes. Striking associations between dinitrochlorobenzene responses and tumor stage, tumor recurrence and several specific parameters of lymph node stimulation were found, while no correlations were made with the pathologic grade, size or type of tumor, degree of schistosomal infestation or tumor bed inflammation. Purified protein derivative responses showed no correlation with any parameter examined. Patient outcome also showed a good correlation with tumor stage and draining lymph node reaction. These findings indicate that dinitrochlorobenzene skin testing as a presumptive test of cell-mediated immunity may represent a good predictor of clinical outcome in patients with bilharzial bladder cancer, and correlates well with draining lymph node stimulation.

Dinitrochlorobenzene skin test reactivity as a predictor of outcome in transplantation of juvenile onset diabetics.

More than 50% of patients with chronic renal failure will be suppressed in their cell-mediated immune response to 2,4-dinitrochlorobenzene (DNCB). This applies in renal failure attributable to juvenile onset diabetes as well as other types of end stage renal disease. Significantly better kidney survival of both living related and cadaver grafts is seen in diabetic patients who are non-responsive to DNCB. Twelve-month kidney survival for DNCB-negative patients receiving living related allografts is 71% compared with 25% for DNCB-positive patients. Twelve-month kidney survival in cadaver recipients is 39% in DNCB-negative compared with 9% for DNCB-positive patients. Successful second grafts were done in DNCB-negative diabetic patients, however, all second grafts in DNCB-positive patients failed in less than 3 months. DNCB skin test reactivity as a measure of cell-mediated response is a valuable predictor of immunological outcome of transplantation in patients whose renal disease results from juvenile onset diabetes. Patient survival in DNCB nonresponders is nearly twice that of DNCB responders. Differences in outcome following transplantation could not be accounted for by HLA disparity, transfusion history, or other variables known to effect transplant outcome. Kidney and patient survival in DNCB-positive diabetic patients receiving either cadaver or living related allografts is sufficiently low as to identify them as a subpopulation of renal failure patients who should be treated by dialysis, or selected for special protocols which might provide immunological manipulation prior to transplantation to improve their treatment outcome.

Specific red cell adherence test and unspecific immune response in patients with superficial bladder cancer.

ABH antigenicity and unspecific immune response were evaluated in 31 patients with superficial transitional cell carcinoma. 26% of these patients showed a reduced dinitrochlorobenzene (DNCB) reaction. There was no significant difference in the monocyte chemotaxis of patients with benign urological diseases and patients with superficial bladder cancer. However, a significant difference exists versus patients with deeply infiltrating carcinomas. 20 patients revealed a loss of ABH antigens on the initial tumor. During the follow-up of at least 1 year, patients with negative DNCB skin test, reduced monocyte chemotaxis and negative specific red cell adherence test demonstrated a high rate of recurrent tumors and in 1 of 7 a progressive tumor developed.

Varicella-zoster virus infection after marrow transplantation for aplastic anemia or leukemia.

Nearly one-half of marrow transplant recipients who survive at least 6 months develop varicella-zoster virus (VZV) infection. Of 92 cases studied, 82 occurred within the first 12 months after transplant. Only one patient had recurrent infection. Seventy-seven patients had herpes zoster, 22 with subsequent cutaneous dissemination, and 15 had varicella. The overall mortality rate was 8%, and all deaths occurred within 9 months of transplant. Twenty-six of 32 patients studied had significant rises in VZV antibody during recovery. Among patients with acute leukemia, those with syngeneic transplants had a significantly lower incidence of VZV infection than those with allogeneic transplants. Incidence was slightly, but not significantly, decreased among patients with aplastic anemia. In contrast to other infections, the incidence of VZV infection was not influenced by graft-versus-host disease or predicted by the results of dinitrochlorobenzene skin testing.

Kaposi's sarcoma in recipients of renal transplants

The purpose of this study was threefold; to ascertain if immunosuppression may be a factor in the causation of Kaposi's sarcoma, to find out if there is a correlation between abnormalities in in vitro studies of cellular immune function and the extent of the disease, and to analyze the literature on Kaposi's sarcoma arising in renal transplant recipients to determine a management policy for these patients. The charts of 44 patients with Kaposi's sarcoma seen in a 20 year period at The Princess Margaret Hospital were reviewed in a search for evidence of immunosuppression as a possible risk factor. Such evidence was found in seven patients. Four of these seven patients were renal transplant recipients, two had generalized lymphomas and were receiving chemotherapy whereas one had a glioblastoma multiforme and was receiving chemotherapy. Studies of cellular immunity using phytohemagglutinin, conconavalin A, pokeweed mitogen, the mixed leukocyte reaction and dinitrochlorobenzene skin testing, in eight patients with Kaposi's sarcoma, three of whom had previous renal transplants, indicate that a correlation exists between the degree of immunologic deficiency and the extent of the Kaposi's sarcoma. Our seven patients were all of Jewish or Mediterranean ancestry. The four cases of Kaposi's sarcoma arising in renal transplant recipients developed in a population of 100 renal transplant recipients of similar ethnic background (4 per cent). This incidence, when compared with our experience of 40 cases arising in 500,000 people of similar ancestry in the Toronto area, represents a 400 to 500 fold greater incidence in renal transplant recipients than in the control population. A literature review has yielded 12 additional cases of Kaposi's sarcoma developing in renal transplant recipients. On the basis of this review and our own experience we have proposed a management policy for these patients. It is proposed that the etiology of Kaposi's sarcoma is multifactorial and that a combination of immunosuppression and/or immunologic stimulation combined with a hereditary predisposition to the disease are responsible for the major increase in its incidence.

Analysis of Late Infections in 89 Long-Term Survivors of Bone Marrow Transplantation

Eighty-nine patients with aplastic anemia or acute leukemia treated by either syngeneic (13 patients) or allogeneic (76 patients) marrow transplantation who had survived for more than 6 mo were surveyed to determine the incidence of late infections. Most patients (72 % ) had either no infection or very few late infections, and only a minority (28 %) had three or more infections. Eight patients (9 %) died from infection. Bacterial infections of lung, respiratory tract, skin, and blood represented more than half of the 152 infections encountered. Gram-positive cocci represented one-third of the documented infecting organisms. Varicella-zoster (VZ) infections were seen in 22 % of all patients.Each affected patient had only a single episode of VZ infection. Fungal infections and interstitial pneumonia were uncommon. By the use of a proportional hazards regression model we attempted to identify clinical and immunologic factors predictive of and predisposing to late infections. Only one factor was significantly associated with late non-VZ infectons: chronic graft-versus-host disease (C-GVHD). Other factors analyzed, e.g., underlying disease,conditioning regimen, type of transplant,inability to respond to cutaneous dinitrochlorobenzene (DNCB), age, and sex, did not show significant associations. In contrast, VZ infections were not associated with C-GVHD. Negative DNCB skin test reactivity appeared to be the only factor-correlating with VZ infections. The recurrent (and occasionally fatal) infections seen in a minority of long-term survivors after syngeneic and allogeneic marrow transplantation are most likely the result of deficits of humoral and cellular immunity, which in turn are most often associated with C-GVHD.

Immune Response in Bladder Cancer Patients

Patients with various stages of bladder cancer underwent skin testing with dinitrochlorobenzene, recall antigens and Croton oil. In vitro lymphocyte evaluation was performed with T and B cell quantitation, T cell cytotoxicity and non-T cell cytotoxicity. Increasing disease stage was reflected by a greater percentage of negative responses to all skin tests. No response to dinitrochlorobenzene was found in 52 per cent of the patients with superficial tumor and 83 per cent of the patients with metastatic disease failed to respond (p < 0.025). After surgical removal of the bladder cancer in patients with superficial disease there was a significant decrease in negative response (p < 0.05). Skin test response in patients with invasive disease who were tested before and after cystectomy demonstrated no significant differences in responses.Assessment of dinitrochlorobenzene skin test response indicates that 1) dinitrochlorobenzene response is related to stage of disease, 2) survival of patients with metastatic tumor was significantly better if the dinitrochlorobenzene test was positive and 3) bladder cancer alters the non-immune host inflammatory system in addition to the delayed hypersensitivity immune system. Inflammatory (non-immune) function as measured by Croton oil response correlated with stage of disease (p < 0.001) but not with prognosis. None of the recall antigen responses correlated with prognosis. Streptokinase-streptodornase was the only recall antigen that related to tumor stage (p < 0.001). Lymphocyte evaluation indicated that bladder cancer patients, regardless of stage of disease, have significant variability, above and below the norm in T cell percentages and antibody-dependent cytotoxicity when compared to age-matched controls. Phytohemagglutinin-dependent cytotoxicity showed a significantly decreased variability after tumor removal (p < 0.001). Lymphocyte cytotoxicity in bladder cancer is greater than in the non-cancer population. This is particularly true in those with metastatic tumor. After removal of the tumor phytohemagglutinin-dependent cytotoxicity returned toward normal

6. Analysis of late infections in 89 long-term survivors of bone marrow transplantation

Eighty-nine patients with aplastic anaemia or acute leukaemia treated by either syngeneic (13 patients) or allogeneic (76 patients) marrow transplantation who had survived for more than 6 mth were surveyed to determine the incidence of late infections. Most patients (72%) had either no or very few late infections and only a minority (28%) had 3 or more infections. Eight patients (9%) died from infection. Bacterial infections of lung, respiratory tract, skin and blood represented more than half of the 152 infections encountered. Gram-positive cocci represented one-third of the documented infecting organisms. Varicella-zoster (VZ) infections were seen in 22% of all patients. Each affected patient had only a single episode of VZ infection. Fungal infections and interstitial pneumonia were uncommon. By the use of a proportional hazards regression model we attempted to identify clinical and immunological factors predictive of and predisposing to late infections. Only 2 factors were significantly associated with late non-VZ infections; chronic graft-versus-host disease (C-GVHD) and inability to respond to cutaneous dinitrochlorobenzene (DNCB). Other factors analysed, e.g. underlying disease, conditioning regimen, type of transplant, age and sex, did not not show significant associations. In contrast, VZ infections were not associated with C-GVHD. Negative DNCB skin test reactivity appeared to be the only factor correlating with VZ infections. The recurrent (and occasionally fatal) infections seen in a minority of long-term survivors after syngeneic and allogeneic marrow transplantation are most likely the result of immunologic deficits—as indicated by the failure to respond to DNCB—which in turn are most often associated with C-GVHD.

Immunological Studies in Patients with Alopecia Areata

Cellular and humoral immune parameters were studied in 10 patients with alopecia areata totalis and universalis. Trends to low normal immunoglobulins levels and in vitro lymphocyte transformation to concanavalin A were observed. Serum CH-50 levels and skin test responses to mumps, candida, trichophytin and dinitrochlorobenzene (DNCB) not found in vitro. 1 patient with alopecia universalis of 33 years duration developed hair at the site of DNCB skin testing. The findings point to rather subtle immune defects in patients with this disease.

Dinitrochlorobenzene skin test in patients with malignant tumor of the head and neck

Dinitrochlorobenzene skin test in patients with malignant tumor of the head and neck

Local delayed cutaneous hypersensitivity reactions in breast cancer patients with and without removal of axillary lymph nodes

Fifty-five patients were sensitized to dinitrochlorobenzene (DNCB). Two weeks later they were challenged. The minimal concentration yielding 2+ reactivity and one dilution above and below were then applied to the anterior chest wall on both the operated and nonoperated sides. Using multinomial chi-square statistical analysis, we found that the operated and nonoperated sides evidenced equal reactivity. Futhermore, the absence of axillary lymph nodes did not diminish the reactivity in the operated area. These data support the contention that maintenance of local cellular immunity, as assessed by DNCB skin test reactivity, is systemic and counters the argument that regional lymphadenectomy impairs local and/or systemic cellular immunity.