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The role of DNA as the target for pathogenic lupus autoantibodies in systemic lupus erythematosus is equivocal and renal damage may be due to cross-reactivity of lupus Abs with glomerular components. We have previously shown that lupus autoantibodies bind to the laminin component of the extracellular matrix. In the present work, we have analyzed the fine specificity of the interaction of pathogenic murine lupus autoantibodies with this molecule and the effect of inhibiting their binding to laminin during the course of the disease. We have found that pathogenic murine lupus autoantibodies react with a 21-mer peptide located in the globular part of the alpha-chain of laminin. Immunization of young lupus-prone mice with this peptide accelerated renal disease. Analysis of transgenic, congenic, and RAG-1(-/-) mice confirmed the importance of this epitope in the pathogenesis of lupus renal disease. We have synthesized a panel of peptides that cross-react with the anti-laminin Abs and have found that the binding of lupus autoantibodies to the extracellular matrix could be inhibited in vitro by some of these competitive peptides. Treatment of MRL/lpr/lpr mice with these peptides prevented Ab deposition in the kidneys, ameliorated renal disease, and prolonged survival of the peptide-treated mice. We suggest that laminin components can serve as the target for lupus Abs. The interaction with these Ags can explain both the tissue distribution and the immunopathological findings in lupus. Moreover, inhibition of autoantibody binding to the extracellular matrix can lead to suppression of disease.

Among the 130 primary or secondary malignant fibrous histiocytomas of bone diagnosed and treated at Memorial Hospital for Cancer and Allied Diseases during the previous half century, 20 (15.4%) arose as a direct consequence of irradiation. This type is the commonest secondary osseous malignant fibrous histiocytoma at this institution. It affects the ilium, the scapula, and the distal end of the femur most frequently, predominantly in patients whose age peaks in the fifth decade of life, when their sarcomas developed. Grounds for the irradiation were either nonosseous conditions (13 patients) or preexistent skeletal lesions (seven patients). Reasons for the incidental bone irradiation included Hodgkin's disease; carcinoma of cervix, breast, or lung; bilateral retinoblastoma, and others; giant cell tumors predominated among the irradiated skeletal lesions. The mean and the median radiation doses were 6,040 and 5,700 rads, respectively. The latent period between irradiation and the appearance of the bone sarcoma ranged from 4 to 47 years with a mean of 16.5 and a median of 14.5 years, respectively. The cumulative disease-free survival rate at 3 years was 58%. Although all patients who received their radiation therapy for a preexistent bone lesion survived, only 27% of patients whose bone was normal at the time of irradiation are alive and well at the 3-year mark.

From 1968-1976, 412 patients were operated on for rectal cancers. One hundred fifty-six underwent abdominoperineal resection (APR) and 256 underwent low anterior resection (LAR). One hundred ninety-two underwent en bloc pelvic lymphadenectomy in conjunction with their resection, while 220 patients underwent more conservative or conventional resection. Thirty-day hospital mortality was 1.7%. The cancer-related 5-year survival was 58.8% for all patients. The proportion of patients surviving 5 years after LAR (62.8%) was significantly better than those surviving after APR (52.4%), p = 0.008. Statistically significantly superior survival was observed after extended dissection when compared to conventional resections in Dukes' A, B, and C patients as a whole (63.8 and 54.3%) and in Dukes' C patients in particular. Superiority of en bloc pelvic lymphadenectomy versus conventional resection was observed in all cases of Dukes' Stage C, Astler-Coller Stage C1, Level II (adjacent) lymph nodes, and Level I (proximal) lymph nodes and was most effective in combination with sphincter-preserving operations. Patient groups were compared for bias and/or case selection, using both contingency tables and Cox-based multiple covariant linear regression analysis, and none was found. In the face of current adjuvant therapy, which is of questionable benefit and which carries its own treatment morbidity, en bloc pelvic lymphadenectomy is advocated as an adjunct to the curative operations for rectal cancer. To improve the overall benefit, patients can be selected for pelvic lymphadenectomy as an adjuvant to resection when preoperative examination suggests that the rectal cancer penetrates the bowel wall. Accurate preoperative staging may help to define a more restricted group of patients warranting (pelvic lymphadenectomy) (PLND). A control randomized trial of the effectiveness of PLND is appropriate to further test its value.

Since 1927, 130 patients with well-documented malignant fibrous histiocytoma of bone have been diagnosed and treated at Memorial Hospital for Cancer and Allied Diseases. This sarcoma is 10 times less frequent than osteogenic sarcoma in this hospital. It most commonly occurred spontaneously (72%), whereas in the rest (28%) it followed previous radiation or various pre-existent osseous conditions, most often Paget's disease. The appendicular skeleton was the commonest site of involvement. The majority of the patients were middle-aged or older adults with a mean of 40.5 years of age; only 21.5% were 21 years or younger. Histologically, the lesions were subclassified as fibrous (62%), histiocytic or xanthomatous (30%), and malignant giant cell tumor (8%) variants. Older patients were more likely to have a secondary malignant fibrous histiocytoma, especially following radiation or Paget's disease. Overall survival estimates at 2 years and 5 years were 71% and 53%, respectively. Survival was not dependent on the histologic subtype of the lesion, but was strongly influenced by the histologic grade of malignancy. Important prognostic factors were the age of the patients and whether the lesions were primary de novo or secondary sarcomas: the older patients and those with secondary lesions did substantially worse.