The 4-kilodalton (39 to 43 amino acids) amyloid beta protein (beta AP), which is deposited as amyloid in the brains of patients with Alzheimer's diseases, is derived from a large protein, the amyloid beta protein precursor (beta APP). Human mononuclear leukemic (K562) cells expressing a beta AP-bearing, carboxyl-terminal beta APP derivative released significant amounts of a soluble 4-kilodalton beta APP derivative essentially identical to the beta AP deposited in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing full-length beta APP and M17 cells expressing only endogenous beta APP also released soluble 4-kilodalton beta AP, and a similar, if not identical, fragment was readily detected in cerebrospinal fluid from individuals with Alzheimer's disease and normal individuals. Thus cells normally produce and release soluble 4-kilodalton beta AP that is essentially identical to the 4-kilodalton beta AP deposited as insoluble amyloid fibrils in Alzheimer's disease.

Madin-Darby canine kidney (MDCK) cells grown in tissue culture have the morphological properties of distal tubular epithelial cells, form tight junctions, and lack several proximal tubular enzyme markers. Adenylate cyclase in these cells was stimulated by vasopressin, oxytocin, prostaglandins E1 and E2, glucagon, and cholera toxin. Hormone-stimulated adenylate cyclase activity in isolated membrane preparations was dependent on low concentrations of GTP and had the MgCIz and pH optima expected for the kidney enzyme. The results, as well as the demonstration of enhanced hemicyst formation induced by cyclic AMP, suggest that the MDCK cell line has retained the differentiated properties of the kidney epithelial cell of origin.When MDCK cells were injected into baby nude mice, continuous nodule growth was observed until adulthood was attained. Histological studies revealed the presence of two cell types: normal mouse fibroblasts which comprised 80-90% of the solid nodule mass, and MDCK cells, which formed epithelial sheets lining internal fluid-filled glands. Electron microscope analysis showed that the mucosal surfaces of the cells were characterized by microvilli which faced the lumen of the glands, that adjacent MDCK cells were joined by tight junctions, and that the serosal surfaces of the epithelial sheets were characterized by smooth plasma membranes which were lined by a continuous basement membrane. These observations lead to the conclusion that the MDCK cells retain regional differentiation of their plasma membranes and the ability to regenerate kidney tubule-like structures in vivo. KEY WORDS kidney epithelial cells epithelial cell polarization vasopressin prostaglandins E1 and E2cyclic AMP MDCK Processes of central importance to the renal physiologist include: (a) the biogenesis of functional kidney tubules, (b) transepithelial salt and fluid transport, and (c) hormonal regulation of transport functions (10, 34). Attempts to gain information about these processes have been hampered by the cellular complexity of the kidney. In general, it has not been possible to assign specific functions to individual cell types because pure populations of kidney-derived primary cell cul-J. CELL BIOLO6V 9 The Rockefeller University Press 9

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Two hundred twenty four dairy cattle (6 mo to second calving) representing four breeds (169 Holstein, 24 Guernsey, 19 Jersey, 12 Brown Swiss) were used to determine effects of age, temperature-season, and breed on blood characteristics. A total of 1183 blood samples were collected by jugular venipuncture in the middle of each temperature-season. Covariate age affected blood profile except for hemoglobin, oxyhemoglobin, glutamic-oxalacetic transaminase, and albumin. Temperature-season increased or decreased all measures except enzyme creatine phosphokinase, total creatine phosphokinase, calcium and phosphorus. Years differed for all measures except hemoglobin and oxyhemoglobin. Except for enzyme creatine phosphokinase, total creatine phosphokinase, and phosphorus, breeds differed in other measures. There were interactions between temperature-season and year, temperature-season and breed, and year and breed. Differences among temperature-seasons were not consistent from year to year. Breed differences were not consistent from temperature-season to temperature-season for calcium or protein-bound iodine. Breed differences were not consistent from year to year for glutamic-oxaloacetic transaminase, total protein, albumin, or calcium.

The 4-kd amyloid beta protein (A beta) deposited as amyloid in Alzheimer's disease (AD) is produced and released by normal proteolytic processing of the amyloid beta protein precursor (beta APP) and is readily detected in cerebrospinal fluid (CSF). Here, we present the levels of A beta in CSF from a total of 95 subjects, including 38 patients with AD, 14 with early-onset AD and 24 with late-onset AD, 25 normal control subjects, and 32 patients with other neurological diseases. The level of A beta decreased with normal aging, and there was a significant elevation in the level of A beta in the CSF of early-onset AD patients (4.14 +/- 1.37 pmol/ml, p < 0.01). Neither Mini-Mental State nor Functional Assessment Staging were correlated with the amount of A beta in the CSF. The A beta/secreted form of beta APP ratio was elevated, but the level of alpha 1-antichymotrypsin in the CSF did not correlate with the level of CSF A beta in early-onset AD patients. Thus, the level of A beta in the CSF is elevated in early-onset AD patients and is suggested to be correlated with the pathology in the brain that characterizes AD.