Association of an interleukin abnormality with the T cell defect in Hodgkin's disease

The cellular immune defect in untreated Hodgkin's disease (HD) has long been recognized. This defect appears to be responsible for at least some of the morbidity and ultimately the mortality associated with the disease. In recent years, many studies have shown that the T cell component of the immune response is the apparent site where the defect in HD exists and where the immunoregulatory abnormalities that may account for the deficit are observed. The discovery of the lymphokines and monokines, comprising the human interleukin system, has elucidated some aspects of the regulatory control of the functional pathways involved in T lymphocyte activation and proliferation. The interleukin system can therefore provide the framework to dissect immunodeficiency states, such as that seen in HD. The present study indicates that HD patients' interleukin 1 (IL1) response appears to be normal, as is their T cell proliferative response to exogenous IL2. Interleukin 2 production by HD patients' peripheral blood mononuclear cells, however, is decreased when compared with age/sex-matched controls. The inability to generate IL2 after appropriate stimulation may reflect either a primary cellular defect or a regulatory defect, such as excessive immunosuppression, giving rise to the characteristic T cell hyporesponsiveness seen in HD.     

RECURRENT CEREBRAL ABSCESSES 20 YEARS BEFORE RECOGNITION OF MULTIPLE PULMONARY ARTERIOVENOUS MALFORMATIONS

SUMMARY A case is presented of a patient with multiple pulmonary arteriovenous malformations, which were successfully treated by embolisation.     

Isolation of functionally different human monocytes by counterflow centrifugation elutriation

Human peripheral blood monocytes were isolated by counterflow centrifugation elutriation (CCE). This technique was modified in such a way that various monocyte fractions (viability greater than 99%) could be elutriated by increasing the density of the CCE-medium in steps of 0.0027 g/ml. All monocytes showed the same size distributions as determined by electronic sizing, which indicated that they differed in their density only. Both cytoplasmic esterase and peroxidase activity increased with the density of the cells. Furthermore, the monocytes with the highest density were 2.3-4 times more active in an antibody- dependent cellular cytotoxicity (ADCC) assay than those with the lowest density. In contrast, the monocyte with the highest density were less capable to induce the proliferation of lymphocytes in mixed leukocyte cultures (MLC) than those with the lowest density. This observation could not be attributed to differences in the expression of HLA-DR determinants, since a monoclonal antibody directed against HLA-DR antigens reacted equally well with the monocytes in different fractions. These results provide evidence for the existence of functionally different subsets of monocytes or different states of differentiation or maturation.     

Routine isotropic computed tomography scanning of the abdomen and pelvis

For 30 years, abdominal CT has been imaged and reviewed in the axial plane. It is now possible to carry out isotropic imaging of the whole abdomen and pelvis using a 40‐channel scanner. This allows creation of coronal and sagittal reformats with the same image quality as the axial images. In this study, we present our experience of reviewing routinely coronal and, occasionally, sagittal reformats. We discuss situations where these nonaxial reformats are most beneficial.     

Magnetic resonance imaging of lumbar vertebral apophyseal ring fractures

Posterior lumbar vertebral apophyseal ring fractures are described in three adolescents presenting with severe low back pain, spinal tenderness and lower limb neurological deficit. Magnetic resonance imaging showed severe L4/5 posterior disc protrusion in all three patients. The actual fracture fragment was visualized with difficulty on MRI alone. The diagnosis of apophyseal ring fracture was made by either radiography or CT. Computed tomography delineated the size, shape and site of the fracture fragment. Surgical confirmation was obtained in all cases. Posterior lumbar vertebral apophyseal ring fractures may be difficult to visualize on MR imaging. Careful review of radiographs, supplemented by targeted CT, is necessary for the correct diagnosis and management of this entity.     

Induction of cathepsin D protein during estrogen carcinogenesis: possible role in estrogen-mediated kidney tubular cell damage

We have proposed that an early step in estrogen carcinogenesis in the hamster kidney is tubular damage followed by reparative cell proliferation. This tubular injury is progressive and increases in severity with continued estrogen treatment; one pertinent feature is a marked rise in the number of both secondary and tertiary lysosomes. Data presented herein indicate that cathepsin D, an estrogen-responsive lysosomal proteolytic enzyme, is increased in the kidney following estrogen treatment in the hamster. Three isoforms of cathepsin D were detected in estrogen-treated kidneys, 52, 31, and 27 kDa, the major being 52 kDa. At 1 and 3 months of estrogen treatment, 52-kDa cathepsin D content increased 1.4- to 1.6-fold. These changes coincided with a rise in renal estrogen receptor levels during the same estrogen treatment periods. More pronounced rises in cathepsin D levels, 2.7- and 3.5-fold, were seen after 4 and 5 months of estrogen treatment, respectively. A concomitant, 3.0- to 4.0-fold rise in estrogen receptor content was also observed. At 5 months of estradiol or DES treatment, both 27- and 31-kDa isoforms were present in hamster kidneys, in addition to the 52-kDa form. Neither progesterone nor DHT treatment affected the untreated levels of cathepsin D. Interestingly, either concomitant tamoxifen or DHT and estrogen treatment prevented the rise in cathepsin D and estrogen receptor content observed after estrogen treatment alone. Primary estrogen-induced renal tumors and their metastases exhibited markedly elevated levels of all three isoforms of cathepsin D. Immunohistochemical analysis of cathepsin D in kidney sections confirmed the Western blot findings. These data suggest a novel role for estrogen-induced cathepsin D in the hamster kidney during tumorigenesis; that is, mediating renal tubular damage as a prelude to reparative cell proliferation, thus initiating a multi-step estrogen-driven process which leads to renal tumor formation.