Showing papers by "University of Colorado Denver published in 1990"
TL;DR: It is demonstrated that MAP kinase is only active when both tyrosyl and threonyl residues are phosphorylated and suggested therefore that the enzyme functions in vivo to integrate signals from two distinct transduction pathways.
Abstract: MAP kinase (relative molecular mass, 42,000), a low abundance serine--threonine protein kinase, is transiently activated in many cell types by a variety of mitogens, including insulin, epidermal growth factor, and phorbol esters. In vitro, MAP kinase will phosphorylate and reactivate S6 kinase II previously inactivated by phosphatase treatment. Because many of the stimuli that activate MAP kinase are also stimulators of cell proliferation, and regulation of the cell cycle seems to involve a network of protein kinases, MAP kinase could be important in the transmission of stimuli eventually leading to the progression from G0 to G1 in the cell cycle. Activated MAP kinase contains both phosphotyrosine and phosphothreonine. We report here that MAP kinase can be deactivated completely by treatment with either phosphatase 2A, a protein phosphatase specific for phosphoserine and phosphothreonine, or CD45, a phosphotyrosine-specific protein phosphatase. We demonstrate that MAP kinase is only active when both tyrosyl and threonyl residues are phosphorylated and suggest therefore that the enzyme functions in vivo to integrate signals from two distinct transduction pathways.
1,014 citations
TL;DR: The Organ Injury Scaling Committee of the American Association for the Surgery of Trauma (A.A.T.) has been charged to devise injury severity scores for individual organs to facilitate clinical research, and the following are proposed O.I.S.'s for the Spleen, Liver, and Kidney.
Abstract: The Organ Injury Scaling (O.I.S.) Committee of the American Association for the Surgery of Trauma (A.A.S.T.) has been charged to devise injury severity scores for individual organs to facilitate clinical research. Our first report (1) addressed O.I.S.'s for the Spleen, Liver, and Kidney; the following are proposed O.I.S.'s for Pancreas (Table I), Duodenum (Table II), Small Bowel (Table III), Colon (Table IV), and Rectum (Table V). The grading scheme is fundamentally an anatomic description, scaled from 1 to 5, representing the least to the most severe injury. We emphasize that these O.I.S.'s represent an initial classification system which must undergo continued refinement as clinical experience dictates.
721 citations
TL;DR: Data indicate that B-type cyclin is the other component of MPF besides p34cdc2, for which exogenously added B1 and B2 cyclins are both substrates.
634 citations
TL;DR: AD may be a systemic illness, a primary defect in cytochrome oxidase may be pathogenically important in its production, and the mitochrondrial genes encoding cyto chrome oxidase subunits may be important in producing the defect.
Abstract: We assayed cytochrome oxidase and other electron transport chain activities in platelet mitochondria isolated from patients with Alzheimer's disease (AD). Five of 6 patients had striking reductions of platelet cytochrome oxidase activity (patient mean, 83.72 +/- 82.99 nmol/min/mg; control mean, 167.14 +/- 36.21 nmol/min/mg; n = 8). Other electron transport chain catalytic activities were not significantly different than control values. AD may be a systemic illness, a primary defect in cytochrome oxidase may be pathogenically important in its production, and the mitochondrial genes encoding cytochrome oxidase subunits may be important in producing the defect.
585 citations
Journal Article•
TL;DR: Smokers of pipes and cigars showed a more elevated risk of cancer of the oral cavity and esophagus than did cigarette smokers, and significantly increased risks emerged also in heavy drinkers, deriving predominantly from wine consumption.
Abstract: A hospital-based case-control study of upper aerodigestive tract tumors was conducted between June 1986 and June 1989 in Northern Italy. One hundred fifty-seven male cases of oral cavity cancer, 134 of pharyngeal cancer, 162 of laryngeal cancer, and 288 of esophageal cancer, and 1272 male inpatients with acute conditions unrelated to tobacco and alcohol were interviewed. Odds ratios for current smokers of cigarettes were 11.1 for oral cavity, 12.9 for pharynx, 4.6 for larynx, and 3.8 for esophagus. For all 4 sites, the risk increased with increasing number of cigarettes and duration of smoking habits and, with the exception of esophageal cancer, decreased with increasing age at the start of and years since quitting smoking. Smokers of pipes and cigars showed a more elevated risk of cancer of the oral cavity and esophagus than did cigarette smokers. Significantly increased risks emerged also in heavy drinkers (odds ratio greater than 60 versus greater than or equal to 19 drinks/week = 3.4, 3.6, 2.1, and 6.0 for oral cavity, pharynx, larynx, and esophagus, respectively), deriving predominantly from wine consumption.
574 citations
TL;DR: The Eulerian-Lagrangian localized adjoint method (ELLAM) as discussed by the authors is a space-time extension of the optimal test function (OTF) method that provides a consistent formulation by defining test functions as specific solutions of the localized homogeneous adjoint equation.
414 citations
TL;DR: To examine the potential role of endothelium-derived relaxing factor (EDRF) in regulation of the perinatal pulmonary circulation, the hemodynamic effects of a selective inhibitor of EDRF production, nitro-L-arginine (L-NA), on pulmonary vascular tone and dilator reactivity in the late-gestation ovine fetus and on the pulmonary vasodilation that normally occurs at birth are studied.
Abstract: To examine the potential role of endothelium-derived relaxing factor (EDRF) in regulation of the perinatal pulmonary circulation, we studied the hemodynamic effects of a selective inhibitor of EDRF production, nitro-L-arginine (L-NA), on pulmonary vascular tone and dilator reactivity in the late-gestation ovine fetus and on the pulmonary vasodilation that normally occurs at birth. L-NA infusion decreased pulmonary blood flow from 78 +/- 8 to 65 +/- 6 ml/min (P less than 0.01) and increased pulmonary artery pressure from 48 +/- 2 to 54 +/- 3 mmHg (P less than 0.002, n = 8 animals). To study the selectivity of L-NA on vasodilator responses to endothelium-dependent (acetylcholine) and -independent (atrial natriuretic factor) stimuli, we measured responses to brief infusions of each dilator before and after L-NA treatment. Acetylcholine increased pulmonary blood flow during the control period but not after L-NA treatment. In contrast, L-NA had little effect on the vasodilator response to atrial natriuretic factor. To study the role of EDRF in the transition of the pulmonary circulation from fetal to neonatal conditions, we infused L-NA into the left pulmonary artery immediately before cesarean-section delivery. In comparison with control animals, the rise in pulmonary blood flow at 1 h after delivery was reduced in the L-NA-treated animals (331 +/- 28 in control vs. 185 +/- 16 ml/min in treated, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
412 citations
TL;DR: The renin-angiotensin-aldosterone system is stimulated significantly more in hypertensive patients with polycystic kidney disease than in comparable patients with essential hypertension.
Abstract: Background. A high incidence of hypertension (50 to 75 percent) occurs early in the course of autosomal dominant polycystic kidney disease. Cyst enlargement, causing bilateral renal ischemia and subsequent release of renin, is proposed as the cause of this form of hypertension. Methods. To investigate this hypothesis, we measured plasma renin activity and aldosterone concentrations during short-term and long-term converting-enzyme inhibition in 14 patients with hypertension due to polycystic kidney disease, 9 patients with essential hypertension, 11 normotensive patients with polycystic kidney disease, and 13 normal subjects. The groups were comparable with respect to age, sex, body-surface area, degree of hypertension, sodium excretion, and renal function. Results. During the short-term study, the mean (±SE) plasma renin activity was significantly higher in the hypertensive patients with polycystic kidney disease than in the patients with essential hypertension, in the supine (0.36±0.06 vs. 0.22...
359 citations
TL;DR: It is concluded that medical student abuse was perceived by these students to be a significant cause of stress and should be a major concern of those involved with medical student education.
Abstract: In a survey of the incidence, severity, and significance of medical student abuse as perceived by the student population of one major medical school, 46.4% of all respondents stated that they had been abused at some time while enrolled in medical school, with 80.6% of seniors reporting being abused by the senior year. More than two thirds (69.1%) of those abused reported that at least one of the episodes they experienced was of "major importance and very upsetting." Half (49.6%) of the students indicated that the most serious episode of abuse affected them adversely for a month or more; 16.2% said that it would "always affect them." Students identified various types of abuse and proposed a number of measures for the prevention and management of abuse in medical school. We conclude that medical student abuse was perceived by these students to be a significant cause of stress and should be a major concern of those involved with medical student education. (JAMA. 1990;263:527-532)
351 citations
TL;DR: Porcine cutaneous wounds are used as a paradigm for tissue organization and healing wounds and adjacent normal skin are probed with polyclonal antibodies to fibronectin and fibronECTin (alpha 5 beta 1) receptor to find out how these interactions affect tissue organization.
310 citations
TL;DR: A modified polymerase chain reaction technique by which enteroviral RNA can be amplified, over a few hours, to a level detectable by agarose mini-gel electrophoresis or nucleic acid hybridization or both is described.
Abstract: Enteroviruses are among the most common causes of childhood infection. Current diagnostic techniques are often too slow and too insensitive to benefit the patient optimally. This report describes a modified polymerase chain reaction technique by which enteroviral RNA can be amplified, over a few hours, to a level detectable by agarose mini-gel electrophoresis or nucleic acid hybridization or both. Three oligomeric regions of great homology among the enteroviruses were identified and designated as a potential primer pair and probe. With this combination, all 11 of the enterovirus serotypes tested, representing the major subgroups of these pathogens, were successfully amplified and detected. The sensitivity and rapidity of this new assay speak to its potential clinical applicability in the diagnosis of enterovirus infections.
TL;DR: A screening neurologic examination capable of detecting distal symmetric (sensory) neuropathy in a large population-based study of non-insulin-dependent diabetes mellitus in San Luis Valley, Colorado, in 1984-1986 is described and validated.
Abstract: A screening neurologic examination capable of detecting distal symmetric (sensory) neuropathy in a large population-based study of non-insulin-dependent diabetes mellitus in San Luis Valley, Colorado, in 1984-1986 is described and validated The examination, completed in 279 diabetics and 577 controls, had 90% agreement with a standard neurologic examination completed on a subsample of 38 patients Independent validation of neuropathy status was obtained with the Optacon tactile (vibration) stimulator Mean, age-adjusted vibration threshold was significantly greater in those with neuropathy than in those without The subtests of the examination most sensitive in detecting neuropathy were a combination of a positive history of neuropathy symptoms and decreased or absent deep tendon reflexes in both ankles Age-adjusted prevalence of neuropathy in controls, those with impaired glucose tolerance, and diabetics was 39%, 112%, and 258%, respectively Prevalence odds ratios were 35 and 106 for the presence of neuropathy in persons with impaired glucose tolerance and diabetes, respectively, compared with persons with normal glucose tolerance Neuropathy was significantly associated with age, duration of diabetes, male sex, and glycemic control, but not with Anglo/Hispanic status
TL;DR: There are only minor changes in amino acid concentrations between midgestation and late gestation in normal fetuses with a constant fetal/maternal ratio, and in small-for-gestational-age infants a significant reduction in alpha-aminonitrogen and in most essential amino acids was demonstrable in utero weeks before delivery.
TL;DR: Using three different protocols, it is demonstrated that antibodies to SS-A/Ro, SS-B/La, and U1RNP bind to UVL-irradiated human keratinocytes, suggesting that this antibody binding is an important inducer of antibody dependent keratinocyte damage in photosensitive cutaneous lupus.
TL;DR: Electro electron transport chain activity in platelet mitochondria taken from HD patients indicated that HD may be caused by a mutation in 1 of the nuclear coded subunits of NADH: ubiquinone oxidoreductase.
Abstract: We evaluated electron transport chain activity in platelet mitochondria taken from HD patients All 5 patients studied had striking depressions of NADH: ubiquinone oxidoreductase activity (complex I) (536 ± 291 nmol/min/mg; control mean, 1912 ± 564 nmol/min/mg) Other electron transport chain activities were not significantly different from control values HD may be caused by a mutation in 1 of the nuclear coded subunits of NADH: ubiquinone oxidoreductase
TL;DR: It is proposed that body fluid volume regulation involves dynamic interaction between cardiac output and peripheral arterial resistance and that the elevated glomerular filtration rate and filtered sodium load seen in pregnant women allow increased distal sodium and water delivery despite a decrease in EABV, thus limiting edema formation during gestation.
Abstract: In studies in experimental animals and in edematous patients, the nonosmotic release of vasopressin has been found to be consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. Moreover, the sympathetic nervous system is known to modulate the nonosmotic release of vasopressin and activation of the renin-angiotensin-aldosterone system. These findings led to our proposal that body fluid volume regulation involves dynamic interaction between cardiac output and peripheral arterial resistance. In this context, neither total extracellular fluid volume nor total blood volume are determinants of renal sodium and water excretion. With a decrease in effective arterial blood volume (EABV) initiated by either decreased cardiac output or peripheral arterial vasodilation, the acute response involves vasoconstriction mediated by angiotensin, sympathetic mediators, and vasopressin. The renal vasoconstriction, which accompanies either decreased cardiac output or peripheral arterial vasodilation, causes a decreased distal tubular delivery of sodium and water, thus maximizing the water-retaining effect of vasopressin and impairing normal escape from the sodium-retaining effect of aldosterone. The elevated glomerular filtration rate and filtered sodium load seen in pregnant women allow increased distal sodium and water delivery despite a decrease in EABV, thus limiting edema formation during gestation.
TL;DR: It is shown that the prevalence of H. pylori infection in Thailand is higher than in industrialized countries, and the high infection rate at the orphanage suggests that person-to-person transmission of the bacterium may be occurring.
Abstract: Serologic studies in developed countries indicate that Helicobacter (formerly Campylobacter) pylori infection is uncommon until the third decade of life and achieves a peak prevalence of 50% in the seventh decade. In developing countries the epidemiology of H. pylori has not well been described. A sensitive and specific serologic assay for H. pylori infection was validated in Thai patients also studied by culture and histologic examination of biopsy specimens. The prevalence of H. pylori antibodies in persons from a rural Thai community began early (17.5% of children 5-9 years old), increased to 55% during the third decade of life, and peaked (75%) in the 30- to 49-year age group. At a Bangkok orphanage where enteric infections are hyperendemic, 74% of children 1-4 years old were seropositive. This study shows that the prevalence of H. pylori infection in Thailand is higher than in industrialized countries. The high infection rate at the orphanage suggests that person-to-person transmission of H. pylori may be occurring.
TL;DR: The results indicate that the early high incidence of hypertension in ADPKD correlates with the renal structural abnormalities in this disorder.
TL;DR: There is no difference between OG (using local anesthesia) and PEG with regard to morbidity, mortality, or tube function, and the endoscopic technique does appear to have economic advantage.
TL;DR: A peptide having enzyme-like catalytic activity has been designed and synthesized and is inhibited by ChTr specific inhibitors and is inactive toward benzoyl arginine ethyl ester, a trypsin substrate.
Abstract: A peptide having enzyme-like catalytic activity has been designed and synthesized. Computer modeling was used to design a bundle of four short parallel amphipathic helical peptides bearing the serine protease catalytic site residues serine, histidine, and aspartic acid at the amino end of the bundle in the same spatial arrangement as in chymotrypsin (ChTr). The necessary "oxyanion hole" and substrate binding pocket for acetyltyrosine ethyl ester, a classical ChTr substrate, were included in the design. The four chains were linked covalently at their carboxyl ends. The peptide has affinity for ChTr ester substrates similar to that of ChTr and hydrolyzes them at rates approximately 0.01 that of ChTr; total turnovers greater than 100 have been observed. The peptide is inhibited by ChTr specific inhibitors and is inactive toward benzoyl arginine ethyl ester, a trypsin substrate. The peptide is inactivated by heating above 60 degrees C, but recovers full catalytic activity upon cooling and lyophilization from acetic acid.
TL;DR: It is proposed that dependency on birds for seed dispersal has occurred primarily in subgenusStrobus, because Strobus pines tend more towards winglessness and increased seed size in stressful environments than doPinus pines.
Abstract: Twenty of approximately 100 species of pines (Pinus spp.) have wingless seeds, and 19 of these are in the subgenusStrobus. Eight of the wingless-seedStrobus pines are known to be dispersed by seed-storing corvids, particularly the nutcrackers (Nucifraga spp.), and the other 11 are presumed to be. The principal consequences of these nearly obligate bird-pine mutualisms include tree clustering and a population structure that differs from that of wind-dispersed pines. The wingless-seedStrobus pines in general are typified by ranges that include xeric conditions and/or high elevations, and large seeds, which are considered to be adaptive under either xeric or competitive conditions. The proposed evolutionary scenario for bird dependency begins with the distribution of ancestralStrobus pines into high elevation or semi-desert environments, sympatric with one or more seed-storing corvid forms, and an increase in seed size. We propose that dependency on birds for seed dispersal has occurred primarily in subgenusStrobus, becauseStrobus pines tend more towards winglessness and increased seed size in stressful environments than doPinus pines. Seed winglessness and other bird-pine traits probably arose from a combination of genetic drift in small populations and selection by corvids.
TL;DR: It is concluded that vascular laboratory tests provide a useful, and objective means of determining the prevalence of PAD in a geographically-based population of diabetic and control subjects.
TL;DR: DNA sequence studies of several excision-amplification plasmids demonstrate a common feature to be the presence of short repeated sequences at both termini with a prevalence of GGCGCAAGCTC.
Abstract: The complete 94,192 bp sequence of the mitochondrial genome from race s of Podospora anserina is presented (1 kb = 10(3) base pairs). Three regions unique to race A are also presented bringing the size of this genome to 100,314 bp. Race s contains 31 group I introns (33 in race A) and 2 group II introns (3 in race A). Analysis shows that the group I introns can be categorized according to families both with regard to secondary structure and their open reading frames. All identified genes are transcribed from the same strand. Except for the lack of ATPase 9, the Podospora genome contains the same genes as its fungal counterparts, N. crassa and A. nidulans. About 20% of the genome has not yet been identified. DNA sequence studies of several excision-amplification plasmids demonstrate a common feature to be the presence of short repeated sequences at both termini with a prevalence of GGCGCAAGCTC.
TL;DR: Identification of factors predictive of the ultimate outcome provide a basis for either continued efforts with management of Kasai's operation or for early referral for liver transplantation.
TL;DR: It is proposed that apoB translocation across the endoplasmic reticulum determines its entry into two functionally distinct pools; the intralumenal trypsin-insensitive pool participates in the assembly of very low density lipoprotein; the trypsIn-accessible nontranslocated cytoplasmic pool is shunted into a degradative pathway.
TL;DR: A link between cell cycle control and cell growth control is provided and changes in cell adhesion and the cytoskeleton in mitosis may be regulated indirectly by MPF via protooncogene activation.
Abstract: The control of cell proliferation involves both regulatory events initiated at the plasma membrane that control reentry into the cell cycle and intracellular biochemical changes that direct the process of cell division itself. Both of these aspects of cell growth control can be studied in Xenopus oocytes undergoing meiotic maturation in response to mitogenic stimulation. All mitogenic signaling pathways so far identified lead to the phosphorylation of ribosomal protein S6 on serine residues, and the biochemistry of this event has been investigated. Insulin and other mitogens activate ribosomal protein S6 kinase II, which has been cloned and sequences in oocytes and other cells. This enzyme is activated by phosphorylation on serine and threonine residues by an insulin-stimulated protein kinase known as MAP-2 kinase. MAP kinase itself is also activated by direct phosphorylation on threonine and tyrosine residues in vivo. These results reconstitute one step of the insulin signaling pathway evident shortly after insulin receptor binding at the membrane. Several hours after mitogenic stimulation, a cell cycle cytoplasmic control element is activated that is sufficient to cause entry into M phase. This control element, known as maturation-promoting factor or MPF, has been purified to near homogeneity and shown to consist of a complex between p34cdc2 protein kinase and cyclin B2. In addition to apparent phosphorylation of cyclin, regulation of MPF activity involves synthesis of the cyclin subunit and its periodic degradation at the metaphase----anaphase transition. The p34cdc2 kinase subunit is regulated by phosphorylation/dephosphorylation on threonine and tyrosine residues, being inactive when phosphorylated and active when dephosphorylated. Analysis of phosphorylation sides in histone H1 for p34cdc2 has revealed a consensus sequence of (K/R)S/TP(X)K/R, where the elements in parentheses are present in some but not all sites. Sites with such a consensus are specifically phosphorylated in mitosis and by MPF in the protooncogene pp60c-src. These results provide a link between cell cycle control and cell growth control and suggest that changes in cell adhesion and the cytoskeleton in mitosis may be regulated indirectly by MPF via protooncogene activation. S6 kinase II is also activated upon expression of MPF in cells, indicating that MPF is upstream of S6 kinase on the mitogenic signaling pathway. Further study both of the signaling events that lead to MPF activation and of the substrates for phosphorylation by MPF should lead to a comprehensive understanding of the biochemistry of cell division.
TL;DR: The clinical features and preoperative and postopera tive electrodiagnostic studies were reviewed in two professional pitchers with a suprascapular neuropathy demonstrate that denervation of the infraspinatus and/or supraspInatus muscle is not al ways due to entrapment of the nerve at the suPRascap ular or spinoglenoid notches, as is often proposed.
Abstract: The clinical features and preoperative and postopera tive electrodiagnostic studies were reviewed in two professional pitchers with a suprascapular neuropathy. These studies demonstrate that denervation of the infraspinatus and/or supraspinatus muscle is not al ways due to entrapment of the nerve at the suprascap ular or spinoglenoid notches, as is often proposed. Similar studies in healthy pitchers during spring training and again at midseason demonstrate that slowing of suprascapular nerve conduction is detectable in some cases as the season progresses.Sagittal sections of a cadaver with the arm fixed in the acceleration phase of the pitching motion demon strate five possible sites of trauma to the suprascapular nerve. Mechanisms proposed to explain these progres sive, but potentially reversible, changes include consid eration of biomechanical factors as well as anatomical features. An alternative hypothesis to nerve trauma that explains this symptom complex is intimal damage to the axillary or suprasca...
TL;DR: It is concluded that acute (wasting) and chronic (stunting) malnutrition are common in childhood CLD and that weight/height values underestimate the degree of acute malnutrition compared with TSF thickness, most likely because of the inflated patient weight caused by organomegaly.