During bladder development, undifferentiated mesenchymal and epithelial cells undergo an orderly sequence of differentiation defined by the expression of smooth-muscle (alpha-actin, myosin, vinculin, desmin, vimentin, and laminin) and epithelial (cytokeratins 5, 7, 8, 14, 18 and 19) protein markers. This process requires mesenchymal-epithelial interactions with bladder epithelium (urothelium) necessary for the differentiation of bladder smooth muscle. Peptide growth factors such as keratinocyte growth factor (KGF) and transforming growth factors (TGF) alpha and beta are likely candidates as mediators of these mesenchymal-epithelial interactions. Transcripts for KGF, TGF alpha, and TGF beta are regulated during bladder development and during smooth-muscle hypertrophy secondary to bladder-outlet obstruction. Finally, two experimental bladder models--(1) partial outlet obstruction and (2) regeneration of bladder smooth muscle into an acellular tissue matrix--are described in the context of mesenchymal-epithelial interactions in the bladder.

Embryologically, the urinary bladder is formed from endodermally derived epithelial cells and mesenchymal cells from the urogenital sinus and allantois. Experimentally, we have shown that bladder mesenchyme differentiates into bladder smooth muscle via an unknown signaling mechanism that originates from the urothelium. It is hypothesized that this signaling between the cellular types, occurs via growth factors. Evidence supporting this hypothesis is that a number of known growth factors, such as TGF beta 2 and 3, KGF and TGF alpha, as well as their receptors are regulated as a function of bladder development and are also modulated during experimental bladder outlet obstruction. Furthermore, growth factors most likely affect extracellular matrix degradative proteins which play a role in bladder remodeling during development, as well as in partial outlet obstruction. There is certainly impressive cellular communication that occurs during development and also occurs postnatally; such as during bladder injury. We have recently shown that KGF is directly responsible for the proliferation of urothelium during bladder injury. This normally quiescent cell, which in humans turns over once every six months to a year when injured, has the incredible ability to immediately proliferate covering the exposed areas of bladder muscle and submucosa. This proliferation is due to the direct effects of KGF, a classic paracrine growth factor which is secreted by the stromal compartment of the bladder and acts directly on the urothelium which harbors the receptor. The bladder also has an uncanny ability to regenerate. In a model to study the basic science behind bladder regeneration, a partial cystectomy was performed and an acellular tissue matrix devoid of all cellular elements was sutured to the defect. Within four days, the urothelium completely covered the acellular matrix, and within two weeks native smooth muscle was seen streaming into the acellular matrix in association with a new epithelium. It is hypothesized that cellular interactions between the epithelium and the mesenchyme, as we have shown in bladder differentiation, are encouraging the new growth of smooth muscle. For the bladder to be a safe and effective storage chamber the ideal cellular lining should be urothelium. Cells from the gastrointestinal are not optimal for this purpose since they either secrete or absorb electrolytes. We believe that the cellular interactions that occur between the urothelium and the foreign intestinal stroma will in time change the phenotype of the urothelium. Newer strategies for bladder replacement which take into account cellular signaling are critical for our young patients with neurogenic bladder disorders.

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FIG. 8 REGULATION CONSTANT AVAILABLE FOR NORMAL WW OF GENERATORS the water column to that of the unit, when instability occurred, was about 0.2. This ratio is obviously not the only factor involved, but is believed to be an important one, and the author suspects, from a study of other plants, that not a few units which now operate very sweetly on the line would be unstable if supplying a rheostat load. The problem is analogous to but more complicated than the stability of surge tanks; and the author wishes at this time to bring the phenomenon into the open for discussion. ACKNOWLEDGMENTThe author's thanks are due to Mr. L. F. Harza, who greatly stimulated his interest in turbine performance, and to Mr. George A. Jessop, for suggestions and data. Di iscussionL. F. IIARZA. 8 The author has urged the use of a valuable form of diagram in which to present hydraulic-turbine test data designed to display the characteristics of the turbine vividly and clearly. This form of turbine characteristic curves was used extensively in the first and subsequent editions of a text by Daniel W. Mead, 9 first published in 1908, on which the writer collaborated, except with a natural instead of logarithmic horizontal scale. The logarithmic scale adds little, if anything, to the diagram except the N, lines become straight instead of curved.Many years ago the writer developed standard platting paper for this type of curve with a sufficient range of horizontal and vertical scales so that any turbine then being built could be platted on this paper. 10 The N, lines were curved because of natural scale. The position of the set of turbine curves on the sheet indicated the type of turbine. Thus a turbine of high 8

The author indicates that the contour form of turbine-efficiency diagram has advantages in giving a clearer picture of performance than the usual efficiency curves. An example illustrates that several different variables can be shown on such diagrams. Formulas are derived for finding the discharge diameters of runners and are illustrated by examples. A simple method of determining the mutual influence of turbine speed and water hammer during transient conditions is illustrated by an example. Finally, the operating stability of a water turbine supplying an independent load is brought forward for discussion.