Influence of PUVA and UVB radiation on delayed hypersensitivity in the guinea pig

Exposure of guinea pigs to UVA (320--400 nm) radiation following administration of 8-methoxypsoralen by gavage (referred to by the acronym, PUVA) or exposure to UVB (290--320 nm) radiation, produced suppression of the cutaneous delayed hypersensitivity reaction at the site of exposure to radiation and at distant nonexposed sites. In these experiments, the animals were immunized by injection of dinitrophenyl-bovine gamma-globulin (DNP-BGG) in complete Freund's adjuvant and delayed hypersensitivity responses were provoked by intradermal injections of DNP-BGG, DNP and BGG on the flanks. Exposure to erythemogenic doses of either PUVA or UVB radiation for 7 days prior to immunization and for the 7 days between immunization and challenge (total period of radiation: 14 days) produced inhibiton of responses to each of the test substances. In addition, treatment with erythemogenic doses of PUVA either for 7 days prior to immunization or during the interval between immunization and challenge with DNP-BGG, inhibited the delayed hypersensitivity responses at the site of irradiation and at a nonexposed site. These findings suggest that in vivo exposure to nonionizing radiation leads to both local and systemic alteration of certain immune responses.     

Reduction of the fraction of circulating helper-inducer T cells identified by monoclonal antibodies in psoriatic patients treated with long-term psoralen/ultraviolet-A radiation (PUVA)

Ultraviolet radiation has been found to alter the distribution and function of human lymphocytes. To determine whether photochemotherapy (PUVA) alters circulating levels of T cell subset marker-bearing lymphocytes, cells from 9 patients with psoriasis undergoing PUVA therapy for several years (mean 4.6 +/- 1.4 yr), 17 patients with active untreated psoriasis, and 20 healthy volunteers were reacted with monoclonal antibodies to T cell surface markers, including OKT3 (all peripheral blood T cells), OKT4 (helper/inducer T cells), OKT6 (common thymocytes), and OKT8 (suppressor/cytotoxic T cells), and analyzed by flow cytometry. There were no differences in the distribution of T cell subsets between healthy volunteers and patients with active psoriasis. In contrast, the percentages of lymphocytes reacting with OKT3 and OKT4 were lower (by 16% and 12% percent respectively, p less than 0.0025) in the PUVA-treated patients compared to healthy volunteers or patients with active psoriasis that had not received PUVA therapy. There was no difference in the percentage of OKT8 and OKT6 bearing cells. Squamous cell carcinoma of the skin subsequently developed in 2 of 3 PUVA-treated patients with the lowest percentages of T4-bearing cells. These findings indicate that long-term PUVA therapy is associated with a reduction in circulating helper/inducer T cells. This reduction may have a role in the altered immune function reported in PUVA-treated patients.     

Activity of DSA against anaerobically adapted Mycobacterium bovis BCG in vitro

DSA is a β-sulfonylacetamide with in vitro activity against pathogenic mycobacteria. Although the enzymatic target(s) of DSA has not been identified, studies to date suggest that this class of compounds may interfere directly or indirectly with ATP synthase and other components of the mycobacterial respiratory chain. In this study we further evaluated the in vitro activity of DSA against anaerobically adapted BCG using two established models. DSA killed BCG in the anaerobic Wayne model. Bactericidal activity ranged from >99% to 60%. DSA killed rifampin-tolerant persisters with a reduction in viable counts of 1.5 log₁₀ versus controls. Conclusive identification of the DSA-specific target(s) will permit a better understanding of the unique mechanism of action of this class of compounds against both aerobically growing and anaerobically adapted bacilli in vitro.     

Working memory and processing speed deficits in systemic lupus erythematosus as measured by the paced auditory serial addition test.

As many as 66% of systemic lupus erythematosus (SLE) patients have been reported to have cognitive deficits. These deficits are often associated with information processing speed and working memory. Similarly, processing speed and working memory impairments are the hallmark of cognitive dysfunction in multiple sclerosis (MS). The Paced Auditory Serial Addition Test (PASAT) places high demands on processing speed and working memory. Fisk and Archibald, however, demonstrated that the total score of the PASAT does not accurately reflect impairments in these cognitive processes. They found that MS patients used a chunking strategy to obtain correct responses and reduce the cognitive demands of the task. In the present study, PASAT performance was examined for 45 SLE patients and 27 controls using alternative scoring procedures. Although the total number of correct responses did not differ between SLE and controls at the 2.4 or 2.0 s presentation rates, SLE patients had fewer dyads (correct consecutive responses) than controls at the faster rate, and more chunking responses than controls at both rates. Disease activity, disease duration, depression, fatigue, and corticosteroids could not account for these differences. The findings suggest that SLE patients, like MS patients, chunk responses more often than controls, and that this scoring procedure may better reflect the working memory and processing speed deficits present in SLE.     

Ambulatory blood pressure in patients with occult recurrent coarctation of the aorta

The hypothesis that mild recurrent aortic obstruction produces subtle changes in ambulatory blood pressure was investigated by performing 24-hour monitoring on 11 postoperative coarctation patients. Patients (age 16.1±2.7 years) were compared with normal controls (age 15.7±2.5 years,n=15). Surgery (end-to-end anastomosis) was performed at 6.0±1.0 years of age. There were no significant differences between patients and controls in terms of baseline blood pressure (right arm 123/78±4/3 mmHg versus 120/75±3/2 mmHg) or right leg systolic pressure (125±6 mmHg versus 123±4 mmHg). Of the 11 patients 8 had recoarctation by Doppler study (mean gradient 25.3±2.1 mmHg), 5 of 11 had a postexercise arm-leg pressure difference of>30 mmHg, and 6 patients had aortic diameters at the site of surgery <70% of the descending aortic diameter (by magnetic resonance imaging). There were no significant differences between the coarctation and control groups in terms of mean ambulatory systolic (125±3 mmHg versus 119±2 mmHg) or diastolic (69±2 mmHg versus 72±2 mmHg) pressures throughout the day. However, coarctation patients had a larger number of systolic pressures that exceeded the 95th percentile (18.2±5.6% versus 6.8±1.2%). These labile increases in systolic pressure correlated with residual coarctation (r=0.642,p=0.003). Ambulatory monitoring is a useful tool for detecting and monitoring subtle abnormalities of blood pressure control after coarctation repair.