Impaired cytotoxic T lymphocyte activity in systemic lupus erythematosus following in vitro polyclonal T cell stimulation: a contributory role for non-T cells.

To determine whether non-T cells contribute to impaired generation of nonrestricted cytotoxic T lymphocyte (CTL) activity in human SLE, peripheral blood mononuclear cells (PBMC) and sort-purified T cells from normal subjects and SLE patients were stimulated with anti-CD3 mAb, maintained in IL2, and assayed for cytolytic activity against 51Cr-labeled Daudi target cells. In addition, T cell and non-T cell fractions were isolated from nine pairs of monozygotic (MZ) twins discordant for SLE, reconstituted in a criss-cross pattern, and stimulated and assayed for cytolytic activity. Cytolytic responses were significantly lower in SLE PBMC cultures than in normal PBMC cultures. Addition of SLE serum to normal PBMC cultures did not inhibit generation of normal cytolytic responses, and neither 'resting' SLE PBMC prior to stimulation nor addition of neutralizing anti-IL10 mAb or costimulating anti-CD28 mAb restored generation of SLE cytolytic responses to normal. Nevertheless, despite the significantly greater cytolytic responses in normal PBMC cultures than in SLE PBMC cultures, cytolytic responses in normal purified T cell cultures were only modestly and insignificantly greater than those in SLE purified T cell cultures. Moreover, substitution of 'healthy' non-T cells for SLE non-T cells in four of the nine MZ twin-pairs appreciably enhanced cytolytic responses, and substitution of SLE non-T cells for 'healthy' non-T cells in five of the seven twin-pairs tested appreciably diminished cytolytic responses. Taken together, these results indicate that, in addition to any inherent SLE T cell abnormalities, impaired function of SLE non-T cells contributes to impaired generation of nonrestricted CTL activity.

Are breast implants anticarcinogenic? A 14-year follow-up of the Los Angeles Study.

Despite decades of use, the long-term safety of breast implants in women remains a concern. While the incidence of breast cancer among women has increased dramatically in the past decade, the implant-related risk of carcinoma of the breast only recently has received widespread attention. An additional concern is that the presence of the implant may delay tumor detection. This study allows examination of breast cancer risk and detection issues among patients with long-term exposure. We conducted a record linkage cohort study of cosmetic breast implant patients. We abstracted the records of the private practices of 35 broad-certified plastic surgeons in Los Angeles County, California. We included 3182 white women who received cosmetic breast implants between 1953 and 1980. Spanish-surnamed women, nonresidents of Los Angeles County, and patients with prior subcutaneous mastectomy or breast cancer were excluded. Cancer outcomes through 1991 have been ascertained through record linkage with the Los Angeles County Cancer Surveillance Program. With a median follow-up of 14.4 years, 31 breast cancer cases were observed, compared with 49.2 expected, based on Los Angeles County population-based incidence rates (standardized incidence ratio = 63.0 percent; 95 percent confidence limits: 42.8 and 89.5 percent). The distribution of stage of disease at diagnosis among women with implants did not differ from that of all similar breast cancer patients in Los Angeles County. In Los Angeles County, augmentation mammaplasty patients experience a significantly lower than expected risk of breast cancer and no delay in breast cancer detection after an average of 14.4 years of exposure. While the linkage methodology allows the possibility of failing to detect diagnosed cancer cases and does not permit collection of some pertinent risk factors, the six other published epidemiologic studies on the topic also report breast cancer risk to be at or below the expected rate.

Impaired recovery and cytolytic function of CD56+ T and non-T cells in systemic lupus erythematosus following in vitro polyclonal T cell stimulation. Studies in unselected patients and monozygotic disease-discordant twins.

OBJECTIVE: To determine whether there is impaired generation and cytolytic function of CD56+ T cells and non-T cells in human systemic lupus erythematosus (SLE). METHODS: Peripheral blood mononuclear cells (PBMC) were obtained from 73 patients with SLE, 39 normal controls, and 9 pairs of monozygotic (MZ) twins discordant for SLE. PBMC were stimulated with anti-CD3 monoclonal antibody, maintained in interleukin-2, and assayed for percentages of total CD56+ cells and CD56+ T cells by flow cytometry, and for cytolytic activity against 51Cr-labeled Daudi target cells. RESULTS: Despite normal total cell expansion, the percentages of recovered CD56+ T cells and total CD56+ cells were 1.6-fold and 1.8-fold lower, respectively, in patients with SLE compared with normal controls (P = 0.011 and P < 0.001, respectively). Cytolytic activities of isolated total CD56+ cells and CD56+ T cells and were also reduced in patients with SLE compared with normal controls (P = 0.033). These defects associated with SLE were independent of disease activity and immunosuppressive medications, and they reflected impaired maturation of cytolytic effector cells rather than a deficiency in precursor cell number. In MZ twins discordant for SLE, recovered percentages of CD56+ cells and cytolytic responses were very low in 4 of 8 and 6 of 9 co-twins with SLE, respectively. Cellmixing experiments with the PBMC of the MZ twins demonstrated that the E+ cell fractions (containing all T cells and CD56+ non-T cells) from the co-twins with SLE had decreased ability to generate cytolytic activity compared with the corresponding E+ cell fractions from the healthy co-twins. However, recovered percentages of CD56+ cells and non-T cells and cytolytic responses were also depressed in 4 of 8 and 4 of 9 healthy co-twins, respectively. CONCLUSION: Impaired CD56+ T cell and non-T cell responses are a feature of SLE and may antedate the onset of clinical disease.

Concordance for Hodgkin's disease in identical twins suggesting genetic susceptibility to the young-adult form of the disease.

BACKGROUND: Relatives of young adults with Hodgkin's disease are at increased risk of Hodgkin's disease, and lines of evidence implicate both inheritance and environment. METHODS: We have identified and followed 432 sets of twins affected by Hodgkin's disease. The number of cases of Hodgkin's disease observed before the age of 50 years in the healthy monozygotic and dizygotic twins of the patients with Hodgkin's disease was compared with the number expected from national age-specific incidence rates. RESULTS: None of the 187 pairs of dizygotic twins became concordant for Hodgkin's disease, whereas 10 of the 179 pairs of monozygotic twins did; in 5 of these pairs, the second case appeared after the original ascertainment. During the observation period, 0.1 (monozygotic) and 0.1 (dizygotic) cases in the unaffected twins were expected. Monozygotic twins of patients with Hodgkin's disease thus had a greatly increased risk (standardized incidence ratio, 99; 95 percent confidence interval, 48 to 182), whereas no increase in the risk for dizygotic twins of patients with Hodgkin's was observed. CONCLUSIONS: Genetic susceptibility underlies Hodgkin's disease in young adulthood.

Augmentation mammaplasty and breast cancer: a 5-year update of the Los Angeles study.

We have previously reported on the risk of breast cancer in women during the first few years following cosmetic augmentation mammaplasty and are now presenting results after longer exposure. Long-term carcinogenicity of breast implants in humans has not been assessed previously. We conducted a retrospective cohort study of 3112 patients with a median of 10.6 years of postimplant experience (range 0.1 to 31.7 years). Patients were enrolled from surgeons' records, and cancer outcomes were monitored by the population-based cancer registry serving Los Angeles County. Because of confidentiality concerns, there was no direct patient contact. Twenty-one breast cancers were observed among the implant patients as compared with 31.7 expected, based on Los Angeles County incidence rates [standardized incidence ratio (SIR) = 66 percent, 95 percent confidence limits (CL): 41 percent, 101 percent]. For all other malignancies combined, 45 were observed and 50.0 were expected (SIR = 90 percent, CL: 66 percent, 120 percent). Although the numbers of cases were very small, increased frequencies of lung and vulvar cancers were observed. Based on the evidence to date, we conclude that there is no increase in breast cancer incidence following augmentation mammaplasty.

A case-control study of amyotrophic lateral sclerosis.

The authors conducted a study of 518 amyotrophic lateral sclerosis patients identified between 1977 and 1979 and 518 controls to investigate putative risk factors for this disease. Occupations at risk of electrical exposure were reported more often by patients (odds ratio (OR) = 3.8, 95% confidence interval (CI) = 1.4-13.0) as were electrical shocks producing unconsciousness (OR = 2.8, 95% CI = 1.0-9.9). Although an overall excess of physical trauma associated with unconsciousness was observed in the amyotrophic lateral sclerosis patients (OR = 1.6, 95% CI = 1.0-2.4), the effect was inversely associated with duration of the unconscious episodes, suggesting an effect of recall bias. Only slight differences were found for surgical traumata to the nervous system. Parkinsonism was reported more often among first degree relatives of cases (OR = 2.7, 95% CI = 1.1-7.6). The frequencies of prior poliomyelitis or other central nervous system diseases were similar for patients and controls. Occupational exposure to selected toxic substances was similar for patients and controls except for the manufacture of plastics (OR = 3.7, 95% CI = 1.0-20.5), although few details of these exposures were provided. No differences in occupations with exposure to animal skins or hides were observed.

The relationship between breast cancer and augmentation mammaplasty: an epidemiologic study.

Surgical implantation of breast prostheses for cosmetic purposes has become increasingly popular, and by 1981, it was estimated that three-quarters of a million women had had such an operation. The long-term potential risks, particularly of breast cancer, of such procedures have not been properly investigated. To evaluate the potential breast cancer risk, we have conducted a retrospective cohort study of 3111 women followed through various public and medical records for a total of 18,476 person-years, with a median of 6.2 years per person. The cases of breast cancer were detected by means of a computerized match with the Los Angeles County Cancer Surveillance Program, a population-based cancer registry. Overall, 15.7 breast cancer cases were expected and 9 were observed, a nonsignificant deficit [standardized incidence ratio (SIR) = 57 percent, 95 percent confidence limits: 26 percent, 109 percent]. The cancers were generally diagnosed at an early stage. Among the 573 women aged 40 or older at implantation, 7.1 cases were expected and 8 were observed (SIR = 113 percent). In women whose implants were performed before the age of 40, only 1 case was observed whereas 8.6 cases were expected (SIR = 12 percent, 95 percent confidence limits: 0.3 percent, 65 percent), a significant difference. These data do not support an increased risk of breast cancer following augmentation mammaplasty. The low breast cancer rate in women having augmentation mammaplasty at a young age that many such women may have a reduced amount of breast tissue, but data on this are unavailable.