Gregory T. O'Conor

ENHANCEMENT OF ADENOVIRUS GROWTH IN AFRICAN GREEN MONKEY KIDNEY CELL CULTURES BY SV40.

Summary SV40 enhances the growth of adenovirus 12 in African green monkey kidney (AGMK) cell cultures. In the absence of SV40, adenovirus 12 produces CPE; however, after 72 hours, less than 1% of the cells contain adenovirus particles by electron microscopy, and titrations show no increase in virus. When similar cultures are infected with both SV40 and adenovirus 12, after 72 hours 75% of the cells contain adenovirus particles and there is an increase in virus by titration. A similar enhancement of the growth of adenovirus 5 in AGMK cultures by SV40 has been observed. The development of progressive adenovirus-type cytopathic changes without demonstrable adenovirus particles in cells of AGMK cultures infected with adenoviruses alone suggests the possibility of some type of incomplete virus formation which is able to go to completion in the presence of SV40.

NO EFFECT OF RIBOFLAVINE, RETINOL, AND ZINC ON PREVALENCE OF PRECANCEROUS LESIONS OF OESOPHAGUS: Randomised Double-blind Intervention Study in High-risk Population of China

A randomised double-blind intervention trial was carried out in Huixian, Henan Province, Peoples Republic of China, to determine whether combined treatment with retinol, riboflavine, and zinc could lower the prevalence of precancerous lesions of the oesophagus. 610 subjects in the age group 35-64 were randomised to receive once a week the active treatment (15 mg [50 000 IU] retinol, 200 mg riboflavine, and 50 mg zinc) or placebo. Both at entry to the study and at the end of the treatment, 13.5 months later, the subjects were examined, with an emphasis on signs of vitamin A and riboflavine deficiences, and riboflavine, retinol, beta-carotene, and zinc levels were measured. Compliance was excellent. The final examination, on 567 (93%) subjects, included oesophagoscopy and at least two biopsies. The intervention did not affect the prevalence of oesophageal lesions: after one year, the prevalence of oesophagitis with or without atrophy or dysplasia was 45.3% in the placebo group and 48.9% in the vitamin/zinc treated group.

Antibodies to Epstein-Barr virus (EBV) in American patients with Burkitt's lymphoma.

Twenty‐nine American patients with lymphomas histologically indistinguishable from African Burkitts lymphoma were studied for antibody to the EBV. Antibody titers were higher in the American Burkitt patients than agematched normal controls or patients with acute lymphocytic leukemia (ALL), but they were not as high as the African Burkitt patients. All cases with typical histologic features and adequate pathologic material (including imprints) were positive for antibody to EBV. The young American Burkitt patients (less than 8 years old) had particularly high titers with a geometric mean titer of 1:425 compared to 1:11 for the matched ALL group and 1:4 for the normal controls. These studies indicate that American Burkitt patients, like those in Africa, have elevated EBV antibody levels and provide another similar parameter suggesting that American and African Burkitts lymphoma are the same disease.

Acute Leukemia with Burkitt's Lymphoma Cells and Burkitt's Lymphoma: Simultaneous Onset in American Siblings; Description of a New Entity

Abstract Hematologic neoplasms developed simultaneously in two American siblings. One patient succumbed to a malignant lymphoma, undifferentiated, Burkitts type, a rare tumor in the United States....

Non-Hodgkin's lymphomas. Application of the International Classification of Diseases for Oncology (ICD-O) to the Working Formulation.

International Classification of Diseases for Oncology (ICD‐O) code numbers for the non‐Hodgkins lymphomas (NHL) are assigned to the new Working Formulation (WF). This will facilitate the coding of NHL cases by registrars and pathologists by providing a ready means of translation of terms utilized in most of the existing classification schemes. Additional code numbers and synonyms are suggested to accommodate all of the terms in the six major classification systems curently in use and to permit the coding of immunologic cell type when appropriate tests have been performed. To demonstrate how the assignment of these code numbers can be useful, over 8000 incidence cases from the Surveillance, Epidemiology and End Results (SEER) Program (1977–1980) were coded according to the WF groups and the data analyzed. The prognostic significance of the three major groups in the WF is confirmed for each group in the SEER data and comparisons are discussed with the NCI study.

Primary management of advanced lymphosarcoma with radiotherapy

The results of a pilot study are described using radiotherapy as the primary treatment for patients with advanced lymphosarcoma. Therapy was directed toward the achievement of complete control of disease using total body irradiation (TBI) and total nodal irradiation (TNI). Chemotherapy had restricted use and was reserved for situations where further irradiation appeared to offer limited benefit. All 11 patients with generalized lymph node involvement (Stage III) are currently alive with a median observation of nearly 3 years, and 4 of these have remained continuously free of disease for more than 2 years since initial therapy. Encouraging remission and survival rates have also been observed for patients with generalized lymph node plus bone marrow involvement. In contrast, response to therapy and survival have been very unsatisfactory for patients with extranodal dissemination of disease to sites other than the bone marrow. The clinical staging has correlated better with survival than has the histologic classification based on estimation of tumor cell differentiation. This experience suggests a role for radiotherapy in the primary management of selected patients with advanced lymphosarcoma.

Association of Burkitt's Lymphoma with the Epstein-Barr Virus in Two Developing Countries

The clinical presentation of Burkitts lymphoma (BL) and its association with the Epstein-Barr virus (EBV) varies in different geographic areas, BL in developing countries being “intermediate” between the sporadic and endemic types, both in its clinical presentation and its association with EBV, which varies from 25-80%. In this study we have analysed the clinical features, EBV association, subtype and prevalence of the deleted variant of the Latent Membrane Protein-I (LMP-1) of EBV in forty-two cases from two developing countries- India (n=25) and Argentina (n=17). In both countries the abdomen was the site most commonly involved while jaw involvement was rare. EBV was detected by in-situ hybridization using the EBER-1 RNA probe. 47% of cases from Argentina and 80% of cases from India were EBER positive. EBV typing using EBNA-3C primers showed a predominance of Type A in both countries (India-13/16 and Argentina-7/8). The 30bp deletion of the LMP-I gene was detected in all evaluated cases from Argentina while the wild type of the gene was seen in all the evaluable Indian cases. Our study highlights the similarities and differences in the clinical presentation and EBV association of BL in two developing countries and also indicates that the subtype of EBV and prevalence of the LMP-I deletion may reflect the predominant subtype in a particular population.

Radiotherapeutic Implications of Prospective Staging in Non-Hodgkin's Lymphoma

The natural history of malignant lymphoma is poorly defined in comparison to that of Hodgkins disease. Patients with malignant lymphoma were subjected to rigorous diagnostic evaluation prior to treatment in an attempt to provide a more rational basis for therapy decision-making. Upon completion of staging of 100 consecutive untreated patients, 64% had histologically documented extranodal dissemination, while only 13% had locoregional involvement (Stage I or II) amenable to potentially eradicative radiotherapy techniques as employed for Hodgkins disease. Thus it is apparent that radiotherapy techniques which are effective in Hodgkins disease are inappropriate in many if not most cases of malignant lymphoma.

A study of p53 protein, proliferating cell nuclear antigen, and p21 in Hodgkin's disease at presentation and relapse

About one fourth of patients with Hodgkins disease relapse after therapy. The mechanisms that lead to resistance to treatment in these patients are poorly understood. The authors describe the differential protein expression of p53, proliferating cell nuclear antigen (PCNA), and p21 at initial presentation and relapse, and discuss their role in disease progression and resistance to therapy. Thirty-four patients with Hodgkins disease who had relapsed after standard chemotherapy and radiotherapy regimens were assessed for the expression of p53 protein, PCNA, and p21 protein (waf/cip 1). In 14 of these cases, sequential biopsies performed both at presentation and at relapse were available for the study. Seventy-five percent of the cases were positive for the p53 protein. Tumors at relapse had higher p53 and PCNA scores than those at initial presentation. In the paired samples, a significant increase was noted in the number of p53 and PCNA-positive cells and in the intensity of staining with p53 antibody. Six of seven paired samples tested for p21 showed an increased p21 expression at relapse. These results suggest that, at relapse, Reed-Sternberg (RS) cells and their variants positive for p53, PCNA, and p21 are increased in number and individually have an increased expression of p53, PCNA, and p21 proteins. These findings suggest that therapy failure and relapse may, at least in part, be associated with altered p53, p21, and PCNA pathways. HUM PATHOL 28:549-555. This work was carried out during an exchange fellowship program at the National Cancer Institute, Bethesda. There are no restrictions on its use

Treatment of lymphosarcoma with fractionated total body irradiation.

A series of patients with disseminated lymphosarcoma has been treated with fractionated total body irradiation. The majority of patients experienced excellent objective remissions of disease as indicated by 75 to 100% decrease in the size of the measurable tumor lesions. No gastro‐intestinal, neurologic or other constitutional symptoms resulted from irradiation and the hematopoietic toxicity was minimal. The encouraging initial responses observed and the absence of serious side effects suggest this modality of therapy constitutes a potentially useful tool in the treatment of this disease.