Showing papers by "University of Colorado Denver published in 1988"

Experimental Campylobacter jejuni Infection in Humans

Abstract: Two strains of Campylobacter jejuni ingested by 111 adult volunteers, in doses ranging from 8 x 10(2) to 2 x 10(9) organisms, caused diarrheal illnesses. Rates of infection increased with dose, but development of illness did not show a clear dose relation. Resulting illnesses with strain A3249 ranged from a few loose stools to dysentery, with an average of five diarrheal stools and a volume of 509 mL. Infection with strain 81-176 was more likely to cause illness, and these illnesses were more severe, with an average of 15 stools and 1484 mL of total stool volume. All patients had fecal leukocytes. The dysenteric nature of the illness indicates that the pathogenesis of C. jejuni infection includes tissue inflammation. Ill volunteers developed a serum antibody response to the C. jejuni group antigen and were protected from subsequent illness but not infection with the same strain.

Insulin-stimulated MAP-2 kinase phosphorylates and activates ribosomal protein S6 kinase II

Abstract: Ribosomal protein S6 is a component of the eukaryotic 40S ribosomal subunit that becomes phosphorylated on multiple serine residues in response to a variety of mitogens, including insulin, growth factors, and transforming proteins of many oncogenic viruses. Recently, an activated S6 kinase (S6 KII) has been purified to homogeneity from Xenopus eggs1, and characterized immunologically2 and at the molecular level3. Purified S6 KII can be deactivated in vitro by incubation with either protein phosphatase 1 or protein phosphatase 2A. Reactivation and phosphorylation of S6 KII occurs in vitro with an insulin-stimulated micro-tubule-associated protein-2 (MAP-2) protein kinase which is itself a phosphoprotein that can be deactivated by protein phosphatase 2A. These studies suggest that a step in insulin signalling involves sequential activation by phosphorylation of at least two serine/threonine protein kinases.

Assessing frontal lobe functioning in children: Views from developmental psychology

Abstract: This review presents the potential contribution of developmental psychology to a more complete understanding of the nature of frontal lobe functioning in children. The cognitive construct of “executive function” has been adopted as a possible behavioral marker of prefrontal functioning from infancy through childhood. Instead of focusing exclusively on mature, adult‐level functioning of the frontal lobes, our article reviews evidence for the view that frontally mediated executive functions emerge in the first year of life and continue to develop at least until puberty, if not beyond. A key theme in this review is that measures used to detect executive functions must be developmentally appropriate, and suggestions regarding viable executive function measures are offered. The contribution of the animal models tested by Diamond and Goldman‐Rakic to our understanding of rudimentary executive functions in infancy is discussed. Another behavioral domain, self‐control, is proposed as a possible source of frontal ...

Purification of maturation-promoting factor, an intracellular regulator of early mitotic events

Abstract: Maturation-promoting factor causes germinal vesicle breakdown when injected into Xenopus oocytes and can induce metaphase in a cell-free system. The cell-free assay was used to monitor maturation-promoting factor during its purification from unfertilized Xenopus eggs. Ammonium sulfate precipitation and six chromatographic procedures resulted in a preparation purified greater than 3000-fold that could induce germinal vesicle breakdown within 2 hr when injected into cycloheximide-treated oocytes. Proteins of 45 kDa and 32 kDa were correlated with fractions of highest activity in both assays. These fractions contained a protein kinase activity able to phosphorylate the endogenous 45-kDa protein, as well as histone H1, phosphatase inhibitor 1, and casein. The highly purified preparations described here should help to identify the mechanism of action of maturation-promoting factor and to elucidate the role of protein kinases in the induction of metaphase.

Von Hippel–Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma

Abstract: Von Hippel-Lindau disease (VHL) is an autosomal dominant disorder with inherited susceptibility to various forms of cancer, including hemangioblastomas of the central nervous system, phaeochromocytomas, pancreatic malignancies, and renal cell carcinomas. Renal cell carcinomas constitute a particularly frequent cause of death in this disorder, occurring as bilateral and multifocal tumours, and presenting at an earlier age than in sporadic, non-familial cases of this tumour type. We report here that the VHL gene is linked to the locus encoding the human homologoue of the RAF1 oncogene, which maps to chromosome 3p25 (ref. 4). Crossovers with the VHL locus suggest that the defect responsible for the VHL phenotype is not a mutation in the RAF1 gene itself. An alternative or prior event to oncogene activation in tumour formation may be the inactivation of a putative 'tumour suppressor' which can be associated with both the inherited and sporadic forms of the cancer. Sporadic renal cell carcinomas have previously been associated with the loss of regions on chromosome 3p (refs 5, 6). Consequently, sporadic and VHL-associated forms of renal cell carcinoma might both result from alterations causing loss of function of the same 'tumour suppressor' gene on this chromosome.

Pathogenesis of sodium and water retention in high-output and low-output cardiac failure, nephrotic syndrome, cirrhosis, and pregnancy (2)

Abstract: This article has analyzed the pathogenesis of sodium and water retention in several circumstances. The initiator of retention has been proposed to be either a fall in cardiac output (e.g., low-output cardiac failure and vasoconstrictor hypovolemic nephrotic syndrome) or peripheral arterial vasodilatation (e.g., high-output cardiac failure, cirrhosis, arteriovenous fistula, and pregnancy). In the only state discussed, in which the kidney is diseased and not merely responding to extrarenal reflexes--i.e., nephrotic syndrome--intrarenal mechanisms may predominate and lead to expansion of the arterial vascular tree and suppression of the renin-angiotensin-aldosterone system (i.e., hypervolemic nephrotic syndrome). Otherwise, when kidneys are healthy, either a fall in cardiac output or peripheral arterial vasodilatation may diminish arterial vascular filling and thereby initiate a series of hemodynamic and hormonal events that result in renal sodium and water retention (Fig. 7). Finally, the approach presented in this article should be considered to be a vantage point from which to evaluate states of sodium and water retention, but not to be an exclusive position.

Respiratory Syncytial Virus Infection in Children With Bronchopulmonary Dysplasia

Abstract: Little is known about the risk of severe illness from respiratory syncytial virus infection in children with bronchopulmonary dysplasia A prospective study was done of the natural history of respiratory syncytial virus infection in 30 children less than 2 years of age with bronchopulmonary dysplasia who were in a home oxygen program Surveillance to identify children with acute respiratory symptoms was done by weekly telephone interview Symptomatic children were examined, oxygen saturation was determined by oximetry, and nasopharyngeal lavage fluid was collected for virus cultures and rapid respiratory syncytial virus antigen tests During the 4-month study period (December to April), 27 children had one or more acute respiratory illnesses, and respiratory syncytial virus developed in 16/27 (59%) Passive smoking and greater than or equal to four members in the home increased the risk of symptomatic respiratory syncytial virus (P less than 01 and P less than 03, respectively) Of 16 children, 11 (69%) required hospitalization Of the 11 hospitalized children with respiratory syncytial virus, nine were either still receiving oxygen at home or required oxygen therapy within the previous 3 months v none of five nonhospitalized children (P less than 005) Five of the hospitalized children were greater than 12 months of age and five had respiratory syncytial virus infection previously that had been confirmed by culture results Hospitalizations were prolonged and complicated Seven of 11 children were hospitalized for greater than 1 week; four were admitted to the intensive care unit; four were treated with ribavirin aerosol, and two needed mechanical ventilation There were no deaths(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced Risk of IDDM Among Breast-Fed Children: The Colorado IDDM Registry

Abstract: The hypothesis that breast-feeding can provide protection against the development of insulindependent diabetes mellitus (IDDM) and would, therefore, be less common among subjects with IDDM was tested with a retrospective design. Cases ( n = 268) were selected from the Colorado IDDM Registry and the Barbara Davis Center for Childhood Diabetes (Denver, CO). Two control groups were recruited, one from physicians9 practices throughout Colorado ( n = 291) and the second through random-digit dialing from the Denver area ( n = 188). Cases were less likely to have been breast-fed than controls after adjustment for birth year, maternal age, maternal education, family income, race, and sex [adjusted odds ratio (OR) = 0.70; 95% confidence interval (Cl) = 0.50–0.97]. This finding was consistent for both control groups and by birth-year intervals. A greater decrease in risk of IDDM was seen among subjects who had been breast-fed to an older age (for breast-feeding duration of ≥12 mo, adjusted OR = 0.54, 95% Cl = 0.27–1.08). The amount of IDDM that might be explained by breast-feeding habits (population percentage attributable risk) ranged from 2 to 26%, varying according to the breast-feeding prevalence reported in other studies. Replication of this work in different populations, controlled for the strong secular trends in breast-feeding habits, is critical before the hypothesis of protection is accepted.

Guidelines for improving the use of antimicrobial agents in hospitals: a statement by the Infectious Diseases Society of America.

Abstract: This is the first in a series of reports being prepared by the Infectious Diseases Society of America (IDSA) that will deal with issues in antimicrobial therapy. Antimicrobial agents are often used inappropriately [1-19]. This may be attributed to their success in the treatment and prevention of serious infections, the complexity of the decision-making process in patients with infectious diseases, the desire of physicians to use the very best drugs available, and the promotional efforts of pharmaceutical manufacturers. The reasons for concern about excessive use of antibiotics are the burden of resistant organisms, adverse reactions to these drugs, and excessive costs. The issue of cost containment has become increasingly important as government and third-party payers seek to control expenditures in the health care system. The members and fellows of the IDSA were polled to obtain their views on the issues of optimum usage of antibiotics in hospitals. They registered concern about excessive and often inappropriate use of antibiotics in hospitals [20]. Effective antimicrobial agents are an essential part of patients' care. Intensive use of antimicrobial agents is associated with development of resistant strains [21-33], and excessive use increases costs unnecessarily [34-46]. Nevertheless, new agents are welcome that fill important therapeutic needs and overcome problems of resistance. To help hospitals provide the very best agents for care of patients by their staff, assure quality of care, and decrease the problems of emergence of resistant strains, the IDSA has prepared a series of general guidelines for evaluating and con-

Echocardiographic findings in autosomal dominant polycystic kidney disease.

Abstract: Echocardiography, including Doppler analysis, was performed to assess the prevalence of cardiac abnormalities in 163 patients with autosomal dominant polycystic kidney disease, 130 unaffected family members, and 100 control subjects In these three groups, the prevalence of mitral-valve prolapse was 26, 14, and 2 percent, respectively (P less than 00005) A higher prevalence of mitral incompetence (31, 14, and 9 percent, respectively; P less than 0005), aortic incompetence (8, 3, and 1 percent, respectively; P less than 005), tricuspid incompetence (15, 7, and 4 percent, respectively; P less than 002), and tricuspid-valve prolapse (6, 2, and 0 percent, respectively; P less than 002) was also found in the patients with polycystic kidney disease These findings reflect the systemic nature of polycystic kidney disease and support the hypothesis that the disorder involves a defect in the extracellular matrix and the cardiac abnormalities are an expression of that defect

Xanthine oxidase-derived hydrogen peroxide contributes to ischemia reperfusion-induced edema in gerbil brains.

Abstract: The contribution of toxic O2 metabolites to cerebral ischemia reperfusion injury has not been determined. We found that gerbils subjected to temporary unilateral carotid artery occlusion (ischemia) consistently developed neurologic deficits during ischemia with severities that correlated with increasing degrees of brain edema and brain H2O2 levels after reperfusion. In contrast, gerbils treated just before reperfusion (after ischemia) with dimethylthiourea (DMTU), but not urea, had decreased brain edema and brain H2O2 levels. In addition, gerbils fed a tungsten-rich diet for 4, 5, or 6 wk developed progressive decreases in brain xanthine oxidase (XO) and brain XO + xanthine dehydrogenase (XD) activities, brain edema, and brain H2O2 levels after temporary unilateral carotid artery occlusion and reperfusion. In contrast to tungsten-treated gerbils, allopurinol-treated gerbils did not have statistically significant decreases in brain XO or XO + XD levels, and reduced brain edema and brain H2O2 levels occurred only in gerbils developing mild but not severe neurologic deficits during ischemia. Finally, gerbils treated with DMTU or tungsten all survived, while greater than 60% of gerbils treated with urea, allopurinol, or saline died by 48 h after temporary unilateral carotid artery occlusion and reperfusion. Our findings indicate that H2O2 from XO contributes to reperfusion-induced edema in brains subjected to temporary ischemia.

The glandular odontogenic cyst: an apparent entity

Abstract: This article reports 8 examples of a rare cyst of the jaws that appears to be a distinct entity and which we have named glandular odontogenic cyst because of its unusual histopathological features. This lesion occurs over a wide age range in both sexes, tends to recur, and may become very large. However, one example in this series remained small over a period of 9 years; another, somewhat atypical example, was associated with an ameloblastoma.

Diffuse Lewy body disease and progressive dementia.

Abstract: Thirty cases of diffuse Lewy body disease (DLBD) have been reported, primarily by neuropathologists, but an associated clinical syndrome has not been clearly defined. Four recent cases have led us to examine the clinicopathologic correlations. Patients are usually elderly, with symptoms lasting from 1 to 20 years. Progressive dementia or psychosis is typically the first and most prominent feature. Parkinsonian signs, initially mild or absent, become common eventually, and rigidity is usually severe. Involuntary movements, myoclonus, quadriparesis in flexion, orthostatic hypotension, and dysphagia have also been noted. Classic, concentric Lewy bodies are found profusely in the brainstem, basal forebrain, and hypothalamic nuclei, while less well defined "Lewy-like" bodies occur in limbic structures and in deep neocortical layers. In addition, focal spongiform changes in the mesial temporal lobe were found in two of our cases. We suggest that DLBD may be another specific cause of progressive dementia.

Correlation of neuropsychological and MRI findings in chronic/progressive multiple sclerosis

Abstract: Sixty patients with chronic/progressive MS received a newly assembled neuropsychological screening battery (NSB) and a brain MRI. A neuroradiologist blinded to NSB findings quantified cerebral lesions on MRI. We developed weighted brain area lesion scores according to number and size of cerebral lesions. Patients who were impaired on NSB testing had a significantly higher mean bihemispheric lesion score (X = 26.1) than those who were unimpaired (X = 17.4); this MRI lesion rating score correlated significantly with the cognitive summary score of the NSB (r = 0.35,p

Neuron-Glia Interrelations

Abstract: Considerable progress in our understanding of neuron and glial cell interrelationships has emerged during the last decade from in vitro and in vivo studies. Neural culture systems have provided powerful tools to delineate cellular and molecular events. Moreover, the advances in development of immunocytochemical and biochemical specific cell markers has made possible the characterization of complex cell behaviors. Glial cells actively participate in several aspects of neuronal growth and differentiation both by providing cell-cell contact interactions and by secreting neuronal growth-promoting factors. In turn, neurons influence the cellular behavior of both astrocytes and oligodendrocytes, primarily by secreting substances into the microenvironment. Such substances as neurohormones and neurotransmitters have been shown to affect several glial functions including electrophysiological responses, energy metabolism, and ionic homeostasis. In several instances these effects appear to be mediated through receptors on glial cells. Astrocytes actively participate in the regulation of the ionic environment. They take up and release several neurotransmitter substances and can modulate the concentration of a neurotransmitter substance at the synaptic cleft and thus monitor neuronal activity. The evidence of neuron-astroglia synaptic contacts supports the view that such contacts are present during early neuroembryogenesis and thus may provide contact signals for neuronal growth. The process of myelination in the CNS appears to be regulated by both neuronal signals to the oligodendrocyte and also intrinsic programming in the oligodendrocytes to produce myelin components. The prevailing view that astrocytes impede regeneration appears to be shifting towards a more favorable notion of the role of these cells in promoting this process. Of interest is the concept that there is a critical period in the ability of astrocytes either to enhance regeneration or to form a gliotic scar and impede this process. The role of glial cells in the aging process of the neuron is only beginning to be appreciated. If glial cells are actively involved in the regulation of the microenvironment, then it follows that any changes in the behavior of glial cells with aging will ultimately affect neuronal function. It is abundantly clear from in vitro studies that glial cells are pluripotential cells with several functional capabilities. Their responsiveness to an environment in which neurons are maturing as compared to an environment where neurons are injured or aging clearly portrays the multifunctional role of the astrocyte.(ABSTRACT TRUNCATED AT 400 WORDS)

Vitamin E Deficiency and Neurologic Disease

Abstract: During the recent resurgence of interest in the clinical uses of vitamin E, one of the major foci of attention has been the neurologic role of vitamin E in humans. Studies in patients with secondary vitamin E deficiency, caused by fat malabsorption disorders and total parenteral nutrition lacking an adequate supply of vitamin E, have elucidated a clinical disorder and histologic lesions of the nervous system and muscle that closely resemble those of experimental vitamin-E-deficient animal models. Investigations of the primary form of human vitamin E deficiency, the isolated vitamin E deficiency syndrome, have further substantiated the relationship between neurologic dysfunction and human vitamin E deficiency. It is now clear that vitamin E is an essential nutrient necessary for the optimal development and maintenance of the integrity and function of the human nervous system and skeletal muscle. The task for future study is to determine the mechanism by which vitamin E deficiency causes degeneration of selective regions of the nervous system and to investigate possible benefits of vitamin E supplementation in other neurologic disorders. In addition, further study of the isolated vitamin E deficiency syndrome promises to teach us more about normal physiologic mechanisms of vitamin E absorption and transport in humans.

Xanthine oxidase produces hydrogen peroxide which contributes to reperfusion injury of ischemic, isolated, perfused rat hearts.

Abstract: Three lines of investigation indicated that hydrogen peroxide (H2O2) from xanthine oxidase (XO) contributes to cardiac dysfunction during reperfusion after ischemia. First, addition of dimethylthiourea (DMTU), a highly permeant O2 metabolite scavenger (but not urea) simultaneously with reperfusion improved recovery of ventricular function as assessed by ventricular developed pressure (DP), contractility (+dP/dt), and relaxation rate (-dP/dt) in isolated Krebs-Henseleit-perfused rat hearts subjected to global normothermic ischemia. Second, hearts from rats fed tungsten or treated with allopurinol had negligible XO activities (less than 0.5 mU/g wet myocardium compared with greater than 6.0 mU/g in control hearts) and increased ventricular function after ischemia and reperfusion. Third, myocardial H2O2-dependent inactivation of catalase occurred after reperfusion following ischemia, but not after ischemia without reperfusion or perfusion without ischemia. In contrast, myocardial catalase did not decrease during reperfusion of ischemic hearts treated with DMTU, tungsten, or allopurinol.

Ultrastructure of mouse vallate taste buds: III. Patterns of synaptic connectivity.

Abstract: We have used serial high voltage electron micrographs and computergenerated, three-dimensional reconstructions to study morphological relationships and patterns of synaptic connectivity in taste buds from the circumvallate papillae of the mouse. The intragemmal arborizations of 40 sensory nerve fibers were examined from 7 taste buds that were sectioned serially. We identified the synaptic connections from taste cells onto the reconstructed nerve fibers and classified the presynaptic taste cells based on previously established ultrastructural criteria. From these data we were able to extract the following information for the reconstructed nerve fibers: (1) the morphology of intragemmal nerve fibers and their arborizations within the taste bud, (2) the total number of synaptic connections from taste bud cells onto the nerve fibers, and (3) the taste cell types associated with each of the synapses. Fifty-six synapses were studied. Synapses were often found to be located at either the branch points or terminations of nerve fiber processes. The maximum number of taste cells observed to synapse onto a single nerve fiber was 5. Several nerve fibers had no apparent synapses. Dark cells (type I), intermediate cells, and light cells (type II) all formed synaptic connections with sensory nerve fibers. In no cases did dark cells and light cells synapse onto the same sensory nerve fiber. Our observation that any given nerve fiber receives its synaptic input from morphologically similar taste cells provides evidence for specificity in taste bud synaptic connections. We speculate that the observed pattern of synaptic connections is related to taste bud function. Since all of the synapses onto a given nerve fiber are from morphologically similar taste cells, we postulate that there is a correlation between taste cell morphology and sensory responsiveness. Intracellular electrophysiological studies on taste cells, in which responses to focally applied chemical stimuli are followed by characterization of the ultrastructural features of the same taste cells, will prove or disprove this hypothesis.