The 2S albumin allergens of Arachis hypogaea, Ara h 2 and Ara h 6, are the major elicitors of anaphylaxis and can effectively desensitize peanut-allergic mice.

BACKGROUND: Ara h 2 and Ara h 6, co-purified together in a 13-25 kD fraction (Ara h 2/6; 20 kD fraction) on gel filtration chromatography, account for the majority of effector activity in a crude peanut extract (CPE) when assayed with RBL SX-38 cells sensitized with IgE from human peanut allergic sera. OBJECTIVES: To determine if Ara h 2/6 are the primary peanut allergens responsible for allergic reactions in vivo and to determine if Ara h 2/6 would be sufficient to prevent allergic reactions to a complete CPE. METHODS: An oral sensitization mouse model of peanut allergy was used to assess the activity of Ara h 2/6 (20 kD) and CPE without the 20 kD fraction (CPE w/o 20 kD) for allergic provocation challenge and immunotherapy. The activity of these preparations was also tested in an assay of histamine release from human basophils in whole blood. RESULTS: Compared with mice challenged with control CPE, mice challenged with CPE w/o 20 kD experienced reduced symptoms (P < 0.05) and a smaller decrease in body temperature (P < 0.01). Results with the basophil histamine release assay corroborated these findings (P < 0.01). The mouse model was also used to administer Ara h 2/6 (20 kD) in an immunotherapy protocol, in which peanut-allergic mice treated with the 20 kD fraction experienced significantly reduced symptoms, changes in body temperature, and mast cell protease (MMCP-1) release compared with placebo (P < 0.01 for all parameters). Importantly, immunotherapy with the 20 kD fraction was just as effective as treatment with CPE, whereas CPE w/o 20 kD was significantly less effective for higher dose peanut challenges. CONCLUSIONS AND CLINICAL RELEVANCE: Ara h 2/6 are the most potent peanut allergens in vivo and can be used to desensitize peanut-allergic mice. These results have potential implications for clinical research in the areas of diagnosis and immunotherapy for peanut allergy.

Effector activity of peanut allergens: a critical role for Ara h 2, Ara h 6, and their variants.

RATIONALE: An important property of allergens is their ability to cross-link IgE and activate mast cells and basophils. The effector activity of peanut allergens has not been well characterized. METHODS: Crude extracts of fresh peanut flour were fractionated by gel filtration. Effector function was assayed by measuring degranulation of RBL SX-38 cells sensitized with IgE from individual sera and from pools of sera of peanut-allergic donors. RESULTS: Following gel filtration, 75 +/- 7% of the applied protein and 76 +/- 16% (n=3) of the applied activity (assayed with a pool of 11 sera) were recovered in the resultant fractions. The majority (85 +/- 2%; n=3) of the recovered activity resided in a fraction with a theoretical average molecular weight of approximately 20 kDa and a range of 13-25 kDa. When all the individual fractions were recombined, the measured activity was similar to that of the original extract [140 +/- 43% when measured with a pool of serum (n=2) and 66 +/- 7% when measured with individual sera (n=4)]; when all individual fractions excluding the 20 kDa fraction were recombined, the measured activity was only 8 +/- 2% (n=2) of the original extract when assayed with the serum pool and 10 +/- 4% (n=3) when assayed with the individual sera. Two-dimensional gel electrophoresis of this biologically active fraction revealed >60 protein spots. Analysis of 50 of the most prominent spots by matrix-assisted laser-desorption ionization time-of-flight mass spectrometry and of the full mixture by automated tandem mass spectrometry coupled to online capillary liquid chromatography revealed that >97% of the protein mass consisted of Ara h 2.0101, Ara h 2.0201, Ara h 6 isoforms, and variants of these proteins. CONCLUSIONS: Ara h 2 and Ara h 6 account for the majority of the effector activity found in a crude peanut extract.

Contribution of Ara h 2 to peanut-specific, immunoglobulin E-mediated, cell activation.

BACKGROUND: Ara h 2 is a potent peanut allergen but its contribution to the ability of a crude peanut extract (CPE) to cross-link IgE and activate mast cells has not been rigorously evaluated. OBJECTIVE: To measure the contribution that Ara h 2 makes to the effector function of a CPE. METHODS: Ara h 2 was specifically removed from a CPE as demonstrated by immunoblots, 2D gels, and an inhibitory ELISA. Functional assays of sham-treated and Ara h 2-depleted CPEs were performed with RBL SX-38 cells sensitized with IgE from highly peanut-allergic subjects and with naturally sensitized basophils. RESULTS: Depletion of approximately 99% of the Ara h 2 from the CPE led to an increase in the concentration of the CPE necessary to give 50% of maximal degranulation (EC50) of the SX-38 cells following sensitization with sera that contain anti-Ara h 2 IgE. Assays with a pool of 10 sera showed a small but significant increase in the EC50 following depletion of Ara h 2 (1.65+/-0.15-fold; P<0.05) and assays of seven individual sera showed a similar increase in the average EC50 (1.7+/-0.2-fold; P<0.02). The percent of the anti-peanut IgE that binds Ara h 2 correlated with an increase in the EC50 of the CPE following depletion of Ara h 2 (r=0.83; P<0.02). On the other hand, data from three of these patients studied with a basophil histamine release assay did not show a significant effect of depletion of Ara h 2. CONCLUSION: Based on its ability to cross-link IgE effectively, Ara h 2 is clearly an important peanut allergen. Its ability to cross-link IgE effectively from a specific serum is related to the proportion of anti-Ara h 2 in that serum but Ara h 2 does not account for a majority of the effector activity of the CPE for any of the sera studied.

UsToo PC-SPES surveys: review of studies and update of previous survey results.

In 1997, we resolved to survey UsToo members and other men known at that time to be taking PC-SPES, a Chinese herb combination that contains eight herbs: chrysanthemum, dyers woad, licorice, reishi, san-qi ginseng, rabdosia, saw palmetto, and baikal skullcap. The survey showed positive results, with respondents experiencing a decline in serum prostate specific antigen (PSA), most to the undetectable range. Of these patients, 88% maintained a low PSA concentration, whereas 12% had a rise from nadir. These results made it obvious that we should obtain follow-up reports from the respondents. We therefore conducted a second survey, this time finding 93% of the respondents with positive results and only 7% reporting a rise in PSA after the initial lowering with PC-SPES. Even though there are some side effects, a great majority of men are realizing good PSA control while taking the capsules, and some of the respondents are now into their fourth year of PC-SPES use. Currently, several institutions are investigating the biology of this Chinese herb combination. Although there is some estrogenic effect, there are other potential mechanisms of action to enable this product to control PSA, not only in newly diagnosed cancer, but also in longer-term use.

Survey of UsToo Members and Other Prostate Cancer Patients to Evaluate the Efficacy and Safety of PC-SPES.

Prostate cancer survivors frequently seek natural remedies for elevated or rising PSA concentrations to forestall the necessity for more definitive modalities. PC-SPES is one of the most widely used of the complementary medicines. It consists of eight Chinese herbs, and although it contains no estrogen, it does exhibit some estrogenic effects. For this reason, UsToo was anxious to determine just how successful the product is and whether any side effects are present. A four-page survey form was designed and pretested on a dozen patients. After refinement, the form was sent to 200 PC-SPES users, mostly UsToo members, with anonymity assured. In only five cases did respondents not identify themselves. After 102 responses had been received, a compilation form was designed to simplify computer database entry of the survey results. This produced a spreadsheet of all 102 respondents' categorized answers. Final analysis followed, with emphasis on prostate specific antigen (PSA) concentrations before and after PC-SPES use, quality of life (QoL), side effects, dosage, and relation to concurrent treatment modalities. Graphs were then constructed on each respondent for study of slope data and PSA changes. Twenty respondents provided insufficient data for analysis; the remaining 82 surveys gave us a good picture of PC-SPES usage and results, as well as information on commingling of other modalities with PC-SPES. Beneficial effects were reported by 77% of the respondents, with 23% reporting more limited or marginal results. Side effects reported were breast tenderness and lowered libido, with three respondents also reporting leg edema. There were no reported cases of circulatory problems or thrombosis. Declines in PSA were reported of as much as 70 ng/mL that were sustained for as long as the respondents have been using PC-SPES, approaching 2 years in some cases. No clinically significant adverse effects were observed. For some men, PC-SPES provides an alternative to hormonal therapy; has a palliative effect when used by patients with advanced, metastatic disease; and overall has a reported 77% effectiveness, with 87% effectiveness when recommended dosages are adhered to.

Comparison of perspectives on prostate cancer: analyses of survey data.

OBJECTIVES: Prostate cancer will account for 334,500 new cases and 41,800 deaths among men in the United States in 1997. Patients and physicians are faced with many concerns related to benefits and side effects of alternative treatments, educational needs, emotional support, and costs of care. Support groups for prostate cancer patients have been established to help satisfy needs in these areas. Therefore, we addressed three issues among patients who belong to a prostate cancer support group as well as among a second group of urologists who treat prostate cancer: (1) goals for prostate cancer treatment, (2) information that is given and recalled about the disease and therapy, and (3) extent to which educational and emotional needs are being met. METHODS: Random telephone surveys were made of 1000 men with prostate cancer who belong to the prostate cancer support group US TOO, the largest prostate cancer support group in the United States, and 200 urologists who provide care to men with prostate cancer. The surveys were conducted by the Louis Harris & Associates survey research firm. RESULTS: About four fifths of patients and urologists prefer aggressive therapy for prostate cancer. Patient goals with therapy included preservation of quality of life (45%), extension of life (29%), and delaying disease progression (13%), whereas physicians overwhelmingly focused on treatment efficacy (86%), with side effects (43%) and costs (29%) being secondary considerations. Urologists and patients differed markedly in the description of the patient-physician discussion. Whereas almost 100% of physicians stated that they always discussed important considerations such as options for no therapy, life expectancy with and without therapy, patient preferences, costs, and changes in sexual function, only about one fifth of patients recalled similar discussions. Patients and physicians both believed that physicians were an excellent source of educational support, but often did not report provision of emotional support. Although support groups were viewed as good providers of educational and emotional support by 85% to 90% of patients, physicians appeared to underestimate the benefit of support groups in these areas. CONCLUSIONS: Patients who belong to US TOO have many emotional and educational needs that are not currently being fulfilled by physicians. Although the goals of therapy are viewed similarly by patients and physicians, much of the important cancer- and treatment-related information that physicians report they have provided is not recalled by patients. Policy makers would be wise to devise systematic strategies such as shared decision-making tools and better linkages to support groups to ensure that patients' needs are being met.

Perspectives on prostate cancer treatment: awareness, attitudes, and relationships.

OBJECTIVES: To compare prostate cancer patients' perceptions with those of physicians regarding treatments, awareness, attitudes, and views of the relationships between the two groups. METHODS: One thousand randomly selected members of US TOO International, Inc., and 200 doctors actively involved in the treatment of prostate cancer, were involved in the study. RESULTS: Almost half of the prostate cancer patients surveyed (48%) were diagnosed with the disease between the ages of 60 and 69; almost one-third were over the age of 70 (31%), and one-fifth (21%) younger than 60 years old. Doctors feel more confident than patients that the patients were sufficiently informed to make treatment decisions, although the majority of patients surveyed reported they took a very active or somewhat active role in the treatment decision process. The doctors' recollection of discussing treatment options exceeded the patients' recollections of those discussions. Doctors and patients alike believe support groups, such as US TOO, to be supportive. CONCLUSIONS: Although recollections of treatment discussions differ between doctors and patients, ongoing communication is very important. The majority of patients state they have relied upon several sources for gaining knowledge of their disease and their options, namely, their doctors, other health professionals, and support groups.

Submucous cleft palate.

We review 97 cases of SMCP, 79 of which were operated. The comparative results are presented. For those requiring surgery (i.e. those having hypernasality), it has been our experience that the use of a pharyngeal flap, alone or combined with a palatoplasty, is productive of better speech results than is a palatoplasty alone.