Eradication of tumor colonization and invasion by a B cell-specific immunotoxin in a murine model for human primary intraocular lymphoma

Human primary intraocular lymphoma (PIOL) is predominantly a B cell-originated malignant disease with no appropriate animal models and effective therapies available. This study aimed to establish a mouse model to closely mimic human B-cell PIOL and to test the therapeutic potential of a recently developed immunotoxin targeting human B-cell lymphomas. Human B-cell lymphoma cells were intravitreally injected into severe combined immunodeficient mice. The resemblance of this tumor model to human PIOL was examined by fundoscopy, histopathology, immunohistochemistry, and evaluated for molecular markers. The therapeutic effectiveness of immunotoxin HA22 was tested by injecting the drug intravitreally. Results showed that the murine model resembles human PIOL closely. Pathologic examination revealed that the tumor cells initially colonized on the retinal surface, followed by infiltrating through the retinal layers, expanding preferentially in the subretinal space, and eventually penetrating through the retinal pigment epithelium into the choroid. Several putative molecular markers for human PIOL were expressed in vivo in this model. Tumor metastasis into the central nervous system was also observed. A single intravitreal injection of immunotoxin HA22 after the establishment of the PIOL resulted in complete regression of the tumor. This is the first report of a murine model that closely mimics human B-cell PIOL. This model may be a valuable tool in understanding the molecular pathogenesis of human PIOL and for the evaluation of new therapeutic approaches. The results of B cell-specific immunotoxin therapy may have clinical implications in treating human PIOL.     

The utility of HPV DNA triage in the management of cytological AGC

OBJECTIVE: Given the demonstrated utility of human papilloma virus DNA triage in the management of atypical squamous cells of undetermined significance, this study sought to evaluate the potential role of human papilloma virus DNA testing in the evaluation and management of cytological atypical glandular cells. STUDY DESIGN: Following institutional review board approval, 28 women presenting with cytological atypical glandular cells underwent repeat thin-prep cytology, Hybrid Capture 2 human papilloma virus DNA testing, colposcopic evaluation, Fisher electrosurgical conization, and endometrial sampling. Human papilloma virus test results in each patient were then correlated with histologic lesions, if present. RESULTS: Sixteen of the 28 study patients had pathologic lesions (11/28 high-grade squamous intraepithelial lesion, 3/28 low-grade squamous intraepithelial lesion, 1/28 adenocarcinoma in situ, 1/28 simple endometrial hyperplasia). Human papilloma virus DNA testing was available in 24 of 28 subjects (86%). The sensitivity of human papilloma virus positivity to predict the presence of cervical intraepithelial neoplasia was 100% (confidence interval 77% to 100%), specificity 64% (confidence interval 35% to 85%), positive predictive value 76%, and negative predictive value 100%. Women who tested human papilloma virus positive were 12 times more likely to have cervical intraepithelial neoplasia than women who were human papilloma virus negative (Fisher P<.001). Human papilloma virus positivity was not predictive of endometrial pathology; women who were human papilloma virus positive were less likely to have endometrial pathology than were women who were human papilloma virus negative (risk ratio 1.6, 95% confidence interval 0.01-1.7). CONCLUSION: Atypical glandular cells can represent a variety of lesions. The majority of the lesions will be squamous intraepithelial lesions of the cervix (50%), with high-grade squamous intraepithelial lesion present in 40% of subjects. Human papilloma virus DNA testing is a sensitive test for the presence of squamous intraepithelial lesion, with excellent negative predictive value for the absence of squamous intraepithelial lesion. The results of this study suggest human papilloma virus DNA testing might be an effective screening test in the initial evaluation and management of cytological atypical glandular cells.     

Incest and Child Sexual Abuse

Child sexual abuse was examined nationally and in the Washington, DC and Howard University Hospital area. In an attempt to describe this widespread problem, two case histories are presented which reflect some of the typical characteristics of child sexual abuse cases seen at Howard University Hospital. Pertinent literature is reviewed citing the prevalence rates and the personality and environmental factors which may contribute to the sexual abuse of children in this country. Finally, the role of the physician in identifying and treating the physical and emotional effects of child abuse are discussed.     

Guanosine 5′-Diphosphate, 3′-Diphosphate: Assignment of Structure by 13C Nuclear Magnetic Resonance Spectroscopy

Guanosine tetraphosphate, recently discovered to mediate the regulatory relationship between protein synthesis and RNA accumulation in various bacteria, has been synthesized in vitro in large quantities and analyzed by natural-abundance (13)C nuclear magnetic resonance spectroscopy in order to confirm its structure and establish the positions of phosphate attachment. These studies have established its structure as guanosine 5'-diphosphate, 3'-diphosphate.     

Comparison of the effects of neonatal thymectomy on Plasmodium berghei,Trypanosoma lewisi and Trypanosoma cruzi infection in the albino rat

Summary Neonatally thymectomized COBS albino rats (Charles River) were infected with the pathogenic intraerythrocytic protozoan parasite Plasmodium berghei, or the nonpathogenic extracellular protozoan Trypanosoma lewisi or a pathogenic protozoan having both intra- and extracellular forms, Trypanosoma cruzi. Neonatally thymectomized, sham-operated, and unoperated control rats were challenged with 1.0×10⁶ P. berghei infected erythrocytes at 6, 8 or 12 weeks of age and parasitemia, anemia and mortality were studied. Others were infected with 1.0×10⁶ T. lewisi at 8 weeks of age or 2.0×10⁵ trypomastigotes of T. cruzi at 5–6 weeks of age and parasitemia was investigated. Each age group of neonatally thymectomized rats infected with P. berghei developed significantly higher parasitemias, more severe anemias, and in younger rats, higher mortalities than sham-operated or unoperated controls. Significant differences were observed in the mean parasitemia of neonatally thymectomized and sham-operated or unoperated control rats challenged with T. cruzi. Significant differences were not observed in neonatally thymectomized and sham-operated or unoperated controls challenged with T. lewisi. These observations suggest that in the rat, thymus dependent immune reactions may play a role in acquired immunity to the intracellular blood parasite, P. berghei and to T. cruzi which has an intra- and extracellular stage, but probably does not have a significant role in acquired immunity to the extracellular blood protozoan parasite, T. lewisi.