Frog ventricular cardiac muscle has structural features which set it apart from frog and mammalian skeletal muscle and mammalian cardiac muscle. In describing these differences, our attention focused chiefly on the distribution of cellular membranes. Abundant inter cellular clefts, the absence of tranverse tubules, and the paucity of sarcotubules, together with exceedingly small cell diameters (less than 5 p), support the suggestion that the mechanism of excitation-contraction coupling differs in these muscle cells from that now thought to be characteristic of striated muscle such as skeletal muscle and mammalian cardiac muscle. These structural dissimilarities also imply that the mechanism of relaxation in frog ventricular muscle differs from that considered typical of other striated muscles. Additional ultrastructural features of frog ventricular heart muscle include spherical electron-opaque bodies on thin filaments, inconstantly present, forming a rank across the I band about 150 mgt from the Z line, and membrane-bounded dense granules resembling neurosecretory granules. The functional significance of these features is not yet clear.In frog skeletal muscle, tubular membranebounded spaces, continuous with the interstitial space, penetrate the muscle cell transversely at the level of the Z lines of the myofibrils lying in register with one another. The continuity of the membranes of this transverse tubular system with the cell membrane and of its lumen with the interstitial space of muscle has been clearly demonstrated by Huxley (1) using ferritin.Mammalian heart muscle appears also to possess a transverse tubular system penetrating the muscle cells and having continuities with the cell membrane and interstitial space (2, 3). Rayns et al. (4), using a freeze-etching technique, observed the portals of these transverse tubules on the surface of the cell membrane. The probable role of this internal membrane system in the inward spread of the excitatory signal to the contractile sites in the myofibrils has been elegantly demonstrated by Huxley and Taylor (5) who used microelectrodes to achieve local depolarization of the cell membrane.From these observations and the ones on the role of calcium in the activation of the contractile mechanism (6, 7), a concept of excitation-contraction coupling has emerged which states that the effects of excitation are borne inward across the muscle fiber by the transverse tubular system releasing calcium ion from the sarcoplasmic reticulum surrounding the myofibrils and thereby activating the contractile elements (8).In frog heart muscle, however, Niedergerke 99 on May 12, 2018 jcb.rupress.org Downloaded from

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We induced hypertension by uninephrectomy and treatment with desoxycorticosterone (DOCA) and 1% NaCl in the drinking water in congenic mice that differ in the single gene locus responsible for the presence or absence of the complement component C5 and compared them to uninephrectomized normotensive (no DOCA-NaCl) mice. In contrast to C5-sufficient (C5S) mice. C5-deficient (C5D) mice can neither generate C5a nor assemble C5b-9. After four weeks of treatment, DOCA-C5S and -C5D mice developed similar degrees of hypertension; mice receiving no DOCA remained normotensive. Only hypertensive mice developed glomerular injury. Hypertensive DOCA-C5D mice developed more glomerular capillary loop dilatation and larger glomerular capillary tuft volumes than DOCA-C5S mice (1.0 +/- 0.1 vs. 0.7 +/- 0.03 X 10(6) microns 3, respectively, P less than 0.05). However, DOCA-C5S mice, compared to DOCA-C5D mice, had significantly more glomerular cell proliferation (64.5 +/- 2 vs. 42 +/- 3 nuclei/glomerulus), cell necrosis (injury score 22 +/- 1 vs. 17 +/- 1), extracapillary proliferation (26 +/- 4 vs. 2.5 +/- 2% of glomeruli) and proteinuria (5.9 +/- 0.8 vs. 3.7 +/- 0.5 mg/24 hr; all P less than 0.05). By immunofluorescence microscopy both DOCA-C5S and -C5D had mesangial C3 deposits but only DOCA-C5S mice had C9 deposits. After 16 weeks of DOCA-NaCl C5S mice, in comparison to C5D mice, had more severe glomerulosclerosis (injury score 50 +/- 6 vs. 12 +/- 4), proteinuria (16.6 +/- 0.1 vs. 9 +/- 0.1 mg/24 hr), and renal insufficiency (serum creatinine 0.25 vs. 0.15 mg/dl), all P less than 0.05. These changes occurred despite levels of hypertension that were similar in DOCA-NaCl C5S and C5D throughout the whole study period. We conclude that C5a and/or C5b-9 may play an important role in hypertensive glomerular injury. Moreover, these studies demonstrate that differences in host responses may determine target organ susceptibility to similar injurious mechanisms.

We examined the effects of fixatives and antibody sources on the immunohistologic localization of laminin in normal and cancer-containing human prostates and studied the localization patterns in carcinomas of varying degrees of histologic differentiation. Two different polyclonal antibodies were localized in paraffin-embedded or cryostat sections of fixed (alcohol, formalin, and paraformaldehyde) or unfixed tissue, using the immunofluorescence (IF) or immunoperoxidase (IP) techniques, with positive and negative controls. We found that the IF reactions were more intense in unfixed or alcohol-fixed sections than in paraformaldehyde-fixed specimens. IP reactions were very weak or absent in fixed and paraffin-embedded sections, but pepsin treatment of these sections resulted in more intense and uniform IP reaction products, stronger than in unfixed or ethanol-fixed cryostat sections. With the IP technique, laminin localization was intense and uniform in the basement membranes (BM) of acini, blood vessels, smooth muscle, and nerve fibers in normal prostate, benign hyperplasia (BPH), and well-differentiated carcinomas. The BM of poorly differentiated carcinomas showed widespread absence of laminin reactivity. In normal BPH and well-differentiated tumors, occasional epithelial cells and their surface and acinar lumina had laminin reactivity. However, in higher grade tumors, numerous neoplastic cells had laminin reactivity in cytoplasm, their surface, and secretory material. Some macrophages and neutrophils also contained laminin reactivity, presumably of degraded laminin. In some moderately and poorly differentiated tumors, the BM of small capillaries did not contain laminin. The BM of larger vessels always had laminin reactivity, even in the higher grade tumors.