Comparison of dietary assessment methods in a low-fat dietary intervention program.

The food frequency questionnaire (FFQ) is commonly utilized for assessment of dietary fat intake, but its validity among individuals following a low-fat diet is unclear. We evaluated the agreement of nutrient estimates derived from FFQ, 24-h recall, and 3-day food records obtained from 104 participants in a randomized trial of a low-fat dietary intervention for women at elevated breast cancer risk. Comparisons were made for total calories, percent calories from fat, and total fat after 1 yr. Correlation was assessed using standard methods based on a null hypothesis of no agreement between instruments as well as by a methodology based on a null hypothesis that the instruments should be in agreement. With the use of standard methods, FFQ estimates for women on the low-fat diet were significantly correlated to records only for percent calories from fat (r = 0.39), whereas recall and record estimates were significantly correlated for all three dietary variables. Using the new method, we found no significant correlation between FFQ and either recalls or records for women following a low-fat diet but significant correlation between recall and record estimates for total calories (r = 0.67). Traditional correlation testing may overestimate the extent of agreement in dietary instruments among women on a low-fat diet. We found empirical support for the nontraditional method.

A randomized trial of a low-fat dietary intervention in women at high risk for breast cancer.

A randomized intervention trial of dietary fat reduction to 15% of total calories was initiated in 1987 for women at high risk for breast cancer to determine the feasibility of recruiting and maintaining them on a low-fat diet. The study has enrolled 194 women between the ages of 18 and 67 years who met at least one of three eligibility criteria: 1) a first-degree relative with breast cancer, 2) a P2 or DY Wolfe mammographic pattern, and 3) a prior breast biopsy demonstrating epithelial hyperplasia with or without atypia. Eligible women must also have had diets that contained > or = 30% of calories from fat at entry. Women were randomized to a nonintervention usual diet vs. a 15% low-fat diet. Recruitment was sought through physicians, personal mailings, breast cancer patients, and the news media. Two study sites participated: a large urban hospital affiliated with a university medical center and a community oncology private practice. The results from both institutions were similar and demonstrated that a low-fat dietary plan could be effectively conducted in private as well as academic settings with recruitment tailored to the community where the trial is being conducted. Reduction in dietary fat intake was maximal during the first three months of the dietary intervention and remained stable throughout 12 months of follow-up. Reductions in total calories, weight loss, and percent body fat were minimal. The nonintervention group experienced no major change in their diet. We conclude that it is feasible to recruit women who are at high risk for breast cancer into a dietary intervention trial and with sufficient dietary counseling and motivation on the part of participants, reduction in dietary fat intake can be achieved and maintained. More in-depth analyses of these data will be presented in subsequent reports.

Use of silica gels and mesoporous molecular sieves as supports for the solid-phase Claisen rearrangement.

A series of silica gels and mesoporous molecular sieves differing in both the range of particle size and mean pore size were derivatized with the p-[R,S-alpha-[1-(9H-fluoren-9-yl)-methoxyformamido]-2,4-di methoxybenzyl]- phenoxyacetic acid linker and their loading capacities were measured. Loading capacities ranging between 0.4-0.6 mmol Fmoc/g were achieved. Several of these silica based materials were derivatized with the hydroxymethyl benzoic acid linker and used as supports for the solid phase Claisen rearrangement of a support bound phenyl allyl ether. Both the silica gel and mesoporous supports were heated at 225 degrees C for 3 h to effect the Claisen rearrangement. The results showed that, compared to the same reaction run homogeneously, the silica gel support achieved similar total product yields and ratios for two Claisen products. The mesoporous supports were found to selectively produce one of the Claisen products over the other. Analysis shows that the molecules bound to the mesoporous support are physically further separated from each other as compared to those bound to the silica gel support. A mechanism is presented which accounts for the selectivity of the mesoporous support in forming one Claisen product over the other. The Claisen product was further derivatized to the resulting phenyl ethyl either through a solid phase Mitsunobu reaction on the mesoporous support.

NKR-P1+ cells in the rat uterus: granulated metrial gland cells are of the natural killer cell lineage.

An intriguing component of the maternal response to pregnancy is the differentiation of large numbers of large granular lymphocytes, termed granulated metrial gland (GMG) cells, in the decidua and then in the metrial gland, a structure in the mesometrial triangle unique to rodent pregnancy. We have used the monoclonal antibody 3.2.3 to NKR-P1, a surface molecule involved in triggering natural killer (NK) cells for lysis, to determine the numbers and distribution of NK cells in the nonpregnant rat uterus and during the dramatic changes at implant sites during pregnancy. NKR-P1+ cells were abundant in the nonpregnant uterus, especially in the endometrium. These cells also expressed CD8, CD2, and AsialoGM1. In the subepithelial stroma, the numbers were greatest during proestrus and estrus; in ovariectomized animals, they were severely decreased, but returned to normal with estrogen supplementation. At the time of blastocyst attachment (Day 6), NKR-P1+ cells were few around the implant and in the decidualizing stroma. However, on Day 8, substantial numbers were present in the mesometrial decidua only, and many of these cells expressed the cytolytic protein perforin. By Day 10, NKR-P1+ cells were common within the inner muscle at the base of the mesometrial triangle and in the developing metrial gland, often containing perforin. Larger numbers of perforin+ cells were present in the central decidua towards the ectoplacental cone, and many were weakly NKR-P1+ only. On Day 12, NKR-P1+ cells were almost completely restricted to the metrial gland, with few in decidua, and many were weakly positive. Substantially more perforin-containing cells were seen, indicating that many had lost detectable NKR-P1. This distribution pattern from Days 6-12 is similar to that described for GMG cells and demonstrates that in the rat they belong to the NK cell lineage. These cells were also CD8+ and AsialoGM1+ but negative for CD2 and class II histocompatibility antigens, which is very different from interleukin-2-activated NK cells which they resemble morphologically. The loss during differentiation of NKR-P1 and CD2, which are involved in target adhesion and triggering of NK cells, is consistent with the poor cytolytic capacity reported for these cells.

Serum interleukin 2 (IL-2) levels and prolactin bioactive/radioimmunoassay ratios of women at risk for breast cancer.

In a cohort of women at high risk for developing breast cancer we have observed that 74% of the women with prolactin BA/RIA ratios over 1.4 had detectable levels of IL-2 in their serum (990 +/- 400 mU/ml) and the IL-2 levels were correlated with the prolactin BA/RIA ratio (R = 0.79; P greater than 0.004). Women with BA/RIA ratios were either approximately 1.0 or less than 0.55 had lower levels of serum IL-2 (177 +/- 70 and 130 +/- 40 mU/ml, respectively). Detectable levels of serum IL-2 were found in 58% of those women with BA/RIA ratios of 1.0 and 55% of those with BA/RIA ratios less than 0.55.

Phase II evaluation of aclacinomycin-A in advanced ovarian carcinoma.

Sixteen women with advanced epithelial ovarian carcinoma were treated with Aclacinomycin-A 40 mg/M2 given as a weekly infusion for four consecutive weeks followed by a two week rest period. All had failed prior chemotherapy. No responses were observed. Nausea and vomiting were the most frequent side effect. Myelosuppression was minimal. This dose and schedule of Aclacinomycin-A are not recommended for further trials in ovarian carcinoma.

High-dose ketoconazole therapy in patients with metastatic prostate cancer.

High-dose ketoconazole, 400 mg orally every 8 h, was administered in two groups of patients with metastatic prostate cancer. Group A consisted of 10 patients who had not undergone orchiectomy and Group B, eight patients who had orchiectomy prior to the study. Significant declines in testosterone, androstenedione, and dehydroepiandrosterone levels, reciprocal elevation of the gonadotropin levels (FSH and LH), and a persistent fall in serum acid phosphatase levels were observed in Group A patients. Three Group A patients achieved a partial objective remission (duration 9, 41+, and 69 weeks); four patients, stabilization of their disease for a median of 33.5 weeks (range 16-40+ weeks); and two progressed (The National Prostatic Cancer Project Criteria). Stable disease in two Group B patients (7 and 20 weeks) and progression in four patients were observed. Gastrointestinal irritation was the main toxicity and was similar in both groups. Two Group A patients developed symptomatology consistent with adrenal insufficiency. Ketoconazole can suppress androgen production and has a beneficial role in the hormonal therapy of patients with prostate cancer who have not undergone orchiectomy.

Reaction of the chromatoid body with a monoclonal antibody to a rat histocompatibility antigen.

The monoclonal antibody OX3 against a polymorphic class II antigen encoded by the major histocompatibility locus of the rat has been shown to cross-react with the chromatoid body during spermatogenesis. Using an indirect immunofluorescence assay on frozen, fixed testis sections, the antibody revealed a pattern of fluorescent speckling that correlated with specific stages of spermatogenesis. The positive material first appeared in late pachytene spermatocytes as multiple small spots. Larger dots appeared in all regions containing round spermatids, but, as the spermatids matured, only fine dots were seen. Mature spermatids were negative, as were all early cells (spermatogonia to early pachytene spermatocytes). When suspension of fixed testicular cells were tested, the activity was clearly associated with the chromatoid body adjacent to the nucleus in round spermatids and with multiple smaller structures encircling the nucleus in primary spermatocytes. These associations were confirmed in observations on immature testes at various ages. No reactivity was seen in testes of animals whose testes had previously been irradiated to render them aspermatogenic, nor in grc/grc rats in which spermatogenesis is arrested at the primary spermatocyte stage. Because the expression of this reactivity was seen even in rats that do not express the OX3 antigen on their somatic cells, this antibody should prove useful in determining the structure of this body, its origin and fate, and any possible role it may have in spermiogenesis.

Phase II study of aziridinylbenzoquinone (AZQ: NSC-182986) in the treatment of malignant gliomas recurrent after radiation. Preliminary report.

Seventeen patients with malignant gliomas recurrent after chemotherapy and/or radiation failure were treated with aziridinylbenzoquinone (AZQ) at a dose of 20-15 mg/M2 weekly for four weeks followed by a two week rest. Regression of disease was observed in four patients, 4/17 (24%) for 35, 15+, 40+, and 10 weeks. Toxicity was limited to moderate reversible myelosuppression. AZQ in this dose and schedule has limited but definite activity in patients with malignant gliomas progressive after primary radiation therapy failure.