BAFF overexpression and accelerated glomerular disease in mice with an incomplete genetic predisposition to systemic lupus erythematosus

OBJECTIVE: To determine whether overexpression of BAFF can accelerate the development of systemic lupus erythematosus-associated end-organ disease in hosts with an underlying autoimmune diathesis. METHODS: We introduced a BAFF transgene (Tg) into autoimmune-prone B6.Sle1 and B6.Nba2 mice and evaluated these mice for serologic autoimmunity and renal pathology. RESULTS: B6.Sle1.BAFF and B6.Nba2.BAFF mice, but not non-Tg littermates, frequently developed severe glomerular pathology by 3 months of age. Age-matched B6.BAFF mice, despite renal Ig deposits and increases in B cells and Ig production similar to those in B6.Sle1.BAFF and B6.Nba2.BAFF mice, did not develop glomerular pathology. In B6.Sle1.BAFF and B6.Nba2.BAFF mice, severity of glomerular disease did not obligately correlate with circulating levels of IgG anti-chromatin and/or anti-double-stranded DNA antibodies or with amounts of these autoantibodies deposited in the kidneys. Even in mice with severe glomerular disease, renal tubulointerstitial infiltrates were very limited, and increased proteinuria was not detected. CONCLUSION: BAFF-driven effects on glomerular pathology may be mediated, at least in part, by autoantibodies with specificities other than chromatin and/or by autoantibody-independent means. There is an uncoupling of BAFF-driven precocious glomerular pathology from concomitant development of clinically apparent renal disease, strongly suggesting that BAFF overexpression works in concert with other factors to promote overt renal disease.     

Expression of Ca antigen on human urinary bladder tumors

Flow cytometric measurements of Ca antigen (Ca) visualized by immunofluorescence with Ca1 monoclonal antibody (Ca1) were performed on cells from 26 urinary bladder carcinomas of various histologic grades and DNA ploidy and on 6 samples of morphologically normal urothelium. In normal urothelium and in the 14 diploid tumors the proportion of positively staining cells was low and the differences were not statistically significant. A significant increase in the proportion of fluorescent cells was observed in all but one of the 12 aneuploid tumors. Among the 11 tumors with an increased proportion of positive cells, 7 were invasive. Data recorded in this study suggest that the quantitation of Ca1 fluorescence corresponding to the presence of Ca may prove to be helpful in the evaluation of clinical behavior of bladder tumors.     

Some physiologic characteristics of the electrodermal reflex in the cat

BERNTHAL, P. J. AND M. C. KOSS. Some physiologic characteristics of the electrodermal reflex in the cat. BRAIN RES. BULL. 3(5)437–441, 1978.—The amplitudes of electrodermal reflexes evoked in intact cats were compared under a variety of anesthetic conditions. Electrodermal reflexes were elicited in both decerebrate and spinal preparations with and without anesthesia. Reflex amplitude was significantly depressed in the anesthetized preparation after decerebration or spinal transection. In contrast, spinal transection performed after decerebration in unanesthetized preparations significantly increased the amplitude of the reflex. The evidence presented in this study supports the concept of a primarily inhibitory lower brainstem system with regard to this reflex. The relative stability of the reflex amplitude in the anesthetized cat suggests that this reflex system could be useful in the analysis of the effects of drugs acting on the central nervous system.     

Tracheostomy-related subglottic stenosis: Bacteriologic pathogenesis

Subglottic stenosis carries devastating consequences. Its pathogenesis, and therefore prevention, have thus far eluded precise definition. The following data suggest that tracheostomy results in a contaminated wound, secondarily infecting a larynx which may have been injured by prior intubation, fracture, or surgery. The interpretation of these data is based upon the tested assumption that infection prolongs healing of injured tissue and predisposes to scar and stricture formation. Therefore, the ability to control stomal contamination by the judicious use of topical or systemic antibiotics may play an important role in the prevention of complications in an organ functionally by-passed by the tracheostomy cannula.     

Multispectral analysis of magnetic resonance images

Magnetic resonance (MR) imaging systems produce spatial distribution estimates of proton density, relaxation time, and flow, in a two dimensional matrix form that is analogous to that of the image data obtained from multispectral imaging satellites. Advanced NASA satellite image processing offers sophisticated multispectral analysis of MR images. Spin echo and inversion recovery pulse sequence images were entered in a digital format compatible with satellite images and accurately registered pixel by pixel. Signatures of each tissue class were automatically determined using both supervised and unsupervised classification. Overall tissue classification was obtained in the form of a theme map. In MR images of the brain, for example, the classes included CSF, gray matter, white matter, subcutaneous fat, muscle, and bone. These methods provide an efficient means of identifying subtle relationships in a multi-image MR study.     

Aberrant nuclear/cytoplasmic localization and gene mutation of beta-catenin in classic pulmonary blastoma: beta-catenin immunostaining is useful for distinguishing between classic pulmonary blastoma and a blastomatoid variant of carcinosarcoma

It is now known that gene mutation of beta-catenin with subsequent nuclear/cytoplasmic (N/C) overaccumulation of the protein plays an important role in tumorigenesis of various organs. We recently demonstrated that low-grade adenocarcinoma of the fetal lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA), the epithelial prototype of classic pulmonary blastoma (CPB), shows N/C localization of beta-catenin with genetic mutation. This prompted us to further investigate the state of beta-catenin abnormality in CPB and related neoplasms. We studied 9 lung tumors previously diagnosed as biphasic pulmonary blastoma (PB). Histologically, 4 cases (median age 34 years) were CPB with l-FLAC/WDFA as the epithelial component, whereas 5 cases (median age 65 years) were a variant of carcinosarcoma with high-grade FLAC/clear cell adenocarcinoma with fetal lung features as the epithelial component, which we term the blastomatoid variant of carcinosarcoma (BCS). Immunohistochemically, all 4 CPBs showed aberrant N/C localization of beta-catenin both in the epithelial and mesenchymal components, with especially high staining intensity in the budding glands and morules. In contrast, all 5 BCSs showed preserved or diminished membranous expression and no significant N/C expression of beta-catenin in the epithelial component, and absent or focal N/C expression of beta-catenin in the mesenchymal component. Mutational analysis of exon 3 of the beta-catenin gene revealed that 3 CPBs harbored missense mutations (S29F, S37F, and S37F), whereas none of the 5 BCSs had this mutation. This study suggests that beta-catenin gene mutations may play a role in the tumorigenesis of CPB. Although CPB and BCS have often been grouped together as biphasic PB, they are different entities based on immunohistochemical and molecular analysis of beta-catenin. Immunostaining for beta-catenin is useful for the discrimination.