Glomerular podocyte vacuolation in idiopathic membranous glomerulonephritis.

Vacuoles in glomerular visceral epithelial cells were found in 149 of 254 patients with idiopathic membranous glomerulonephritis (IMGN). In the whole population studied, 115 patients were nephrotic, 88 (76.5%) of which were found to have intraepithelial vacuoles. Fifty (35.9%) of 139 non-nephrotic patients had vacuolated podocytes (p less than 0.01). Vacuolation occurred most frequently in stages II and III of IMGN. A few intraepithelial vacuoles were observed in stage IV. Increase in vacuolation tended to correlate with subepithelial deposits which were larger in size. From these results, we concluded that the appearance of epithelial vacuolation coincides with an increased filtration of protein in IMGN and that it is an important histological marker when diagnosing the level of severity of glomerular lesions. It was not, however, prognostic.     

Differentiation between rat brain and mouse vas deferens delta opioid receptors

Certain enkephalin analogues, including those which contain the conformationally restricted amino acid E-(2R,3S)-cyclopropylphenylalanine [2R,3S)-delta E Phe), have been shown to have high affinity for brain delta opioid receptors but are much less active in mouse vas deferens bioassays. To investigate whether there are differences between delta opioid receptors in brain and mouse was deferens, the ability of a selective delta opioid compound, [D-Pen2,pCl-Phe4,D-Pen5]enkephalin (pCl-DPDPE), and [D-Ala2,(2R,3S)-delta E Phe4,Leu5]enkephalin methyl ester (CP-OMe), to inhibit [3H]pCl-DPDPE binding in both rat brain and mouse vas deferens were measured. pCl-DPDPE recognized brain and mouse vas deferens binding sites with equal affinity, however, CP-OMe showed 33 fold lower affinity in mouse vas deferens compared to brain. This suggests that mouse vas deferens delta opioid receptors may be distinct from brain delta opioid receptors.     

Sialyltransferase activity and hepatic tumor growth in a nude mouse model of colorectal cancer metastases.

Sialyltransferase activity (EC 2.4.99.6) was measured in the microsomal fraction of colorectal cancer cell lines using an assay based on the incorporation of [14C]CMP-sialic acid into asialofetuin. In the poorly differentiated lines MIP101 and Clone A, sialyltransferase activity had a Vmax of 0.36 and 0.31 nmol/mg protein/h, respectively, while the moderately differentiated to well-differentiated cell lines HT-29, CCL188, and CX-1 had Vmaxs of 2.46, 1.05, and 1.24 nmol/mg protein/h, respectively. All cell lines tested had a Km of 15.4 (+/- 0.7)(SD) mumol/liter. The better differentiated cells had higher levels of sialyltransferase activity, which correlated with their higher levels of sialic acid and their enhanced ability to form liver metastases in the nude mouse following intrasplenic injection compared to the poorly differentiated cell lines. Treatment of the cell lines with KI-8110, a CMP-sialic acid derivative which prevents incorporation of sialic acid into glycoconjugates, resulted in reduced formation of hepatic metastases by the colorectal carcinoma cell lines in the nude mouse model. It is suggested that reduced sialylation of adhesion molecules such as carcinoembryonic antigen may change the biology of the tumor cell, one consequence of which is the prevention of implantation of the cells into distant sites, resulting in a reduced incidence of metastases.     

Structure-activity studies of 20-deoxo-20-amino derivatives of tylosin-related macrolides

Reductive amination of the C-20 aldehyde group of tylosin and related macrolides yielded a large series of derivatives with potentially useful antibiotic properties. Evaluation of these new compounds was conducted on the basis of: 1) Broad antimicrobial spectrum in vitro, with particular emphasis on inhibition of Pasteurella multocida and Pasteurella haemolytica; 2) in vivo efficacy, especially when given orally, against P. multocida in experimental infections in chicks; and 3) bioavailability after oral administration to laboratory animals. The most useful activity was found within a series of derivatives produced by reductive amination of desmycosin with secondary amines.     

The Histocompatibility Complex of Rhesus Monkeys. II. A Major Locus Controlling Reactivity in Mixed Lymphocyte Cultures

Rhesus monkeys have a genetic locus which has a major influence on reactivity in mixed lymphocyte cultures (MLR). This MLR locus is closely linked to the RhL–A system², which controls the serologically defined histocompatibility antigens of this species. Three cases of recombination between RhL–A and the MLR region are described. Consequently, the MLR locus is located outside the RhL–A region proper, possibly adjacent to the locus defining the antigens of the 1st series. The recombination frequency between the MLR and RhL–A regions of rhesus monkeys is similar to that found for the analogous systems of man.
Inhibition of MLR can be achieved by pre-incubation of responder or stimulator cells with cytotoxic anti-RhL–A sera. Such inhibition is highly specific and probably caused by an interaction of the sera with RhL–A surface antigens, not with MLR determinants. Yet, there is circumstantial evidence that non-cytotoxic sera can be produced which inhibit MLR, presumably by affecting MLR determinants on the cell surface.
The relevance of MLR to histocompatibility and the genetic control of the immune response of rhesus monkeys to synthetic antigens, are the subjects of current studies which are briefly discussed.