Bernice Kaack

Prevention of pyelonephritis by immunization with P-fimbriae.

P-fimbriae have been found to be a virulence factor in both human and nonhuman primate urinary tract infections caused by Escherichia coli. This is because of bacterial adherence to urothelial cells which is mediated by adherence of fimbriae to a specific glycolipid receptor on the cell membrane of these cells. We purified P-fimbriae for immunization of monkeys. High titers of antifimbrial antibody protected against both acute and chronic pyelonephritis after renal inoculations of P-fimbriate Escherichia coli.

Immunology of pyelonephritis in the primate model. V. Effect of superoxide dismutase.

Ascending acute pyelonephritis was produced in monkeys by infusion of bacteria through a ureteral catheter to the point of intrarenal reflux. This led to a significant inflammatory response with death of renal tubular cells in the area of the tubular granulocytes and bacteria. We gave superoxide dismutase, and found that the inflammatory response was decreased and fewer tubular cells were killed. Ultrastructural change was also decreased in tubular cells adjoining phagocytosing neutrophils. This suggests that renal damage following a bacterial infection may be due to the production and release of superoxide into the tubular lumen during phagocytosis. We believe that it is the initial event which may lead to the eventual loss of renal tissue and function called chronic pyelonephritis.

Experimental Pyelonephritis in the Monkey. VII. Ascending Pyelonephritis in the Absence of vesicoureteral Reflux

Six adult male nonrefluxing monkeys were experimentally infected by inoculation of P-fimbriated E. coli into the bladder. Eight control monkeys were inoculated with a non-P-fimbriated E. coli strain. Inoculation with the P-fimbriated E. coli resulted in marked leukocytosis, prolonged bacteriuria and loss of renal function with a 66 per cent incidence of pyelonephritis. Death secondary to bilateral pyelonephritis was seen in 2 monkeys inoculated with P-fimbriated E. coli. Pyelonephritis was not seen in any of the monkeys inoculated with non-P-fimbriated E. coli. The study shows that ascending pyelonephritis can occur in monkeys in the absence of vesicoureteral reflux.

Immunology of pyelonephritis in the primate model. VI. Effect of complement depletion.

The inflammatory response has been shown to be responsible for the renal damage from bacterial infection. Phagocytic events are responsible for damage to the host as well as the pathogen. In this study we evaluated the effect of complement depletion, in an attempt to decrease chemotaxis and opsonization and thus decrease phagocytosis. Acute renal damage was decreased from both a decrease in inflammatory cells and phagocytic events in the areas of bacterial inoculation.

Lipofuscin: Intra- and Extraneuronal Accumulation and Regional Distribution

The occurrence, progressive accumulation and distribution of lipofuscin or “age” pigment in the human brain have been described by numerous investigators over many years (Hannover, 1842 to Brizzee et al, 1975). It has been known variously as “wear and tear, yellow age, lipo and senile” pigment (Timiras, 1972). The term “lipofuscin” was applied to such pigments very early (Borst, 1922). Lipofuscin accumulates in a progressive manner in neurons of the mammalian nervous system, though the rate of increase varies greatly in various structures. Based on its universal occurrence throughout phylogeny (Dayan, 1971) and its progressive accumulation in organs with such postmitotic cells as the brain (Brizzee et al, 1974) lipofuscin deposition with age has been proposed as a basic “law of cellular aging” (Strehler and Barrows, 1970).

Neurochemical Changes in Composition, Metabolism and Neurotransmitters in the Human Brain with Age

As an interdisciplinary science, gerontology now includes sociology, psychology, physiology biochemistry and morphology. Biological gerontology is regarded as a relatively young discipline. It has a predominant interest in genetic, molecular and cellular mechanisms of aging rather than a cybernetic or systems approach (Sacher, 1968; Dayan, 1972; Timiras, 1972). Attempts to formulate only genetic and molecular hypotheses of aging for the brain a priori exclude reference to possibly equally important other levels of biological and social organization. The brain is uniquely characterized by tissue interdependence, organizational complexity, redundancy and environmental modifiability. This implies that environmental influences on the organization of the brain may be just as significant as the genetic, molecular and cellular changes currently considered as the basic or exclusive sources of biological aging (Strehler and Barrows, 1970; Medvedev, 1972; Orgel, 1973; Marx, 1974).

Changes in Limbic, Neuroendocrine and Autonomic Systems, Adaptation Homeostasis During Aging

In order to survive, all organisms must adapt internally and/ or externally to meet the challenges of the ever-changing environment. The nervous and endocrine systems coordinate and integrate the operation of the other organs of the body to bring about their “homeostatic” adjustments. The Neuroendocrine system is broadly de fined as those structures in the CNS that are concerned with the regulation of endocrine function. Hormones act as regulators of almost all metabolic and functional responses involved in the adaptation of the organism to a complex environment (Prosser, 1958). Thus, the phylogenetic and ontogenetic development of a Neuroendocrine system is indispensable to adaptation since it provides the organism with increasing independence from its physical environment (Mason, 1972; Siegel & Eisenman, 1972).