Sanford Leikin

Cell-mediated Immunity to Respiratory Syncytial Virus Induced by Inactivated Vaccine or by Infection

Extract: Transformation and increased mitotic activity in donor lymphocytes exposed to specific antigens is considered by many to be a manifestation of cell-mediated immunity. In attempts to understand the apparent “sensitization” of individuals to respiratory syncytial virus (RSV) as a result of receiving inactivated RSV vaccine, in vitro lymphocyte transformation studies were carried out on infants who had received inactivated RSV vaccine and on infants who had received a similarly prepared inactivated African green monkey kidney (AGMK) cell-grown parainfluenza type 1 virus vaccine or a trivalent parainfluenza vaccine prepared in hens eggs. Each group included some infants who had, and others who had not, undergone natural RSV infection under our observation before the lymphocyte studies.Lymphocytes were studied from 21 infants and young children who had received the inactivated RSV vaccine, 14 who received a similarly prepared inactivated parainfluenza 1 vaccine, and 5 who received a trivalent parainfluenza vaccine. Twelve of the RSV vaccinees and 14 of the parainfluenza vaccinees had been naturally infected with RSV as indicated by virus recovery and/or antibody rise between the time of vaccination and the lymphocyte studies. In comparing the arithmetic mean for RSV-specific transformation and mitotic activity there was a significant difference between RSV vaccinees and parainfluenza vaccinees whether one compared those who had undergone natural RSV infection or those who had not undergone natural infection. The difference between RSV vaccinees who had not undergone natural RSV infection and RSV-infected parainfluenza vaccinees also was significant. There was a greater level of transformation and mitotic activity in those who had experienced natural infection than those who had not among both RSV vaccinees and parainfluenza vaccinees, but these differences were not significant statistically.Speculation: We take these findings to mean that natural RSV infection probably stimulates a systemic cell-mediated immunity response and that such a response is definitely induced after administration of killed RSV antigen. These findings are consistent with the hypothesis that cell-mediated sensitization may in some way contribute to the altered response to natural infection which occurred after use of inactivated RSV vaccine. Our findings do not support the hypothesis that systemic cell-mediated immunity per se is important in protecting against RSV infection. The findings also suggest the possibility that transplacentally conferred RSV lymphocyte sensitization might play a part in the pathogenesis of nonvaccine related RSV bronchiolitis which characteristically occurs during early infancy, frequently in the presence of measurable serum antibody.

Lymphocyte DNA Synthesis Inhibition

A specific endogenous inhibitor for lymphocyte DNA synthesis that can be isolated from the lymphoid system and which is probably cell specific is described. The inhibitor is thermolabile, is destroyed by trypsin, and has a mass of about 30,000 to 50,000 daltons.

Studies on the pathology of non‐Hodgkin's lymphoma of childhood: I. The role of routine histopathology as a prognostic factor a report from the childrens cancer study group

Between April 1977, and August 1980, the Childrens Cancer Study Group (CCSG) conducted a clinical trial of childhood non‐Hodgkins lymphoma (NHL), randomizing 256 patients to one of two treatment regimens. A 4‐drug regimen (regimen 1, modified cyclophosphamide, Oncorin [vincristine], methotrexate, prednisone [COMP]) was compared with a 10‐drug regimen (regimen 2, modified LSA2‐I2). Using the Rappaport classification, the review pathologist diagnosed the 213 evaluable tissue specimens as follows: lymphoblastic (LC), 73; Burkitts tumor (BT), 40; “undifferentiated” non‐Burkitts type (NB), 67; large cell or “histiocytic” lymphoma (HI), 29; and other types (OT), 4. Concurrence in classification between the review and institutional pathologists was poor when using the above four categories; however, concurrence was 88% between the review pathologist and other hematopathologists, and 99% when classifying the specimens as lymphoblastic or nonlymphoblastic. For patients with nonlocalized disease, this randomized controlled study demonstrated a new important correlation of histopathology with the effectiveness of treatment. When analyzed without stratification into lymphoblastic and nonlymphoblastic types, the two regimens showed identical relapse free survival (RFS) curves for patients with nonlocalized involvement. However, when patients were stratified according to histologic classification, regimen 2 was superior to regimen 1 for patients with lymphoblastic lymphoma, achieving 74% RFS at 30 months compared to 31% for regimen 1 (P = 0.001). Conversely, those with nonlymphoblastic types (BT, NB, HI) treated with regimen 1 had a 58% RFS at 30 months compared to 32% for those treated on regimen 2 (P = 0.01). This study demonstrates that proper, routine histopathologic classification of NHL is the best criterion for choice of therapy in children with nonlocalized involvement. As a result of this study, all patients with nonlocalized disease, diagnosed after August 1980, were no longer randomized but were assigned to the appropriate treatment regimen based on prospective review of histopathology.

In vitro lymphocyte transformation in ataxia telangiectasia

Summary Decreased blast cell transformation wasseen in the lymphocytes from 5 patients with ataxia telangiectasia when they were cultured in vitro with phytohemagglutinin. This seems to be due to a property of the cells and not to a suppressive effect of the serum. It would appear that this is related to other aspects of their deficient immunity.

Immunologic parameters in histiocytosis-X

The immunocompetence of six infants with the clinical form of Letterer‐Siwe disease and seven older children in various phases of histiocytosis was evaluated. In most of the patients, delayed hypersensitivity, lymphocyte blastogenesis to mitogens and allogeneic cells, bactericidal killing, and leukocyte nitroblue tetrozolium dye reduction were found to be within normal limits. One patient with the infantile form of histiocytosis and one older child could not be sensitized to DNFB. The lymphocytes from two infants were hyporeactive to mitogeninduced stimulation. This reverted to normal after chemotherapy was instituted. Decreased immunoglobulin levels were found in two infants. Several patients exhibited elevated immunoglobulin levels. In general, the immunologic abnormalities improved following chemotherapy. No evidence of a combined immunodeficiency disorder was found in either group of patients. It is felt that the immunologic abnormalities which were found were either secondary to malignant cell replacement rather than an underlying cause of the disease.

Liver Resection in Children with Hepatic Neoplasms

In the past ten years, 28 patients with primary tumors of the liver have been treated. There were 11 benign tumors, including four hamartomas, three patients with focal nodular hyperplasia, and two each with congenital cysts and hemangioma. Hamartomas and masses of focal nodular hyperplasia should be excised when possible, but both are benign lesions; therefore life threatening excisions at the porta hepatis should be avoided. Cysts are often resectable, but when occupying all lobes of the liver, they can be successfully managed by marsupialization into the free peritoneal cavity. If resectable, hemangiomas should be removed; when occupying most of the liver as they often do, patients may be subject to platelet trapping or to cardiac failure. In some instances these lesions have been controlled by steroids, radiation therapy or hepatic artery ligation. Of 17 malignant tumors seen, 12 proved to be hepatoblastomas. Nine of the 12 patients underwent liver resection, of whom four are cured, (33%). There were three children with hepatocellular carcinomas and two with embryonal rhabdomyosarcoma. One child from each of these groups is cured by surgical excision. At present the only known cures in children with primary malignant liver neoplasms have been achieved by operative removal.

Differences in transformation of adult and newborn lymphocytes stimulated by antigen, antibody, and antigen-antibody complexes

Abstract It has been proposed that in vitro stimulation of lymphocytes by antigen-antibody complexes is due to an immunologically nonspecific action. The lymphocytes of newborn infants and adults were tested for their ability to respond to tetanus and diphtheria toxoid, the respective antitoxins and antigen-antibody complexes. Cord blood lymphocytes failed to transform with these stimulants whereas the lymphocytes of previously immunized adults were transformed by these antigens and the antigen-antibody complexes. In addition, BSA-anti-BSA complex stimulated lymphocytes from ostensibly unsensitized adults but not the cord blood cells. It is concluded from these results that lymphocyte transformation by antigen-antibody complexes is due to a specific acquired immunologic response and that adult individuals may have unknowingly become sensitized to ubiquitous antigens such as BSA.

Pernicious anemia in a young girlassociated with idiopathic hypoparathyroidism, familial Addison's disease, and moniliasis

A girl with familial Addisons disease, idiopathic hypoparathyroidism, and moniliasis developed pernicious anemia at the age of 10 years. Investigations of her gastrointestinal tract including peroral biopsy were performed. Because of the possible immunologic relationship of pernicious anemia and the endocrinopathies, antibody tests against human gastric mucosa and parietal cells were done and found to be negative. Five cases of pernicious anemia associated with one or the other of these endocrinopathies have been previously reported. At the present time the exact relationship between her hematologic and endocrinologic diseases has not been clarified.

Clotrimazole treatment of chronic mucocutaneous candidiasis

An 11-year-old girl with chronic mucocutaneous candidiasis and multiple immunologic defects was treated with a new oral antifungal agent, clotrimazole. Marked improvement of her skin and mouth lesions ensued without evidence of serious toxicity.

Comparison of exchange transfusion and deferoxamine in the treatment of acute iron poisoning

The efficacy of iron removal by deferoxamine, exchange transfusion, and a combination of deferoxamine and exchange transfusion was studied in 3 groups of dogs with severe iron intoxication. The amount of iron excreted in the urine of dogs treated with deferoxamine was minimal. The mean amount of iron removed in the group receiving exchange transfusion alone was 30 times greater than the amount obtained by urinary excretion in the group treated with deferoxamine. Chelation with deferoxamine followed by exchange transfusion did not increase the amount of iron removed by exchange transfusion.