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Showing papers by "University of Colorado Denver published in 1983"


Journal ArticleDOI
22 Jul 1983-Science
TL;DR: The properties, physiological roles, and mechanisms for regulating the four protein phosphatases are reviewed and their roles in controlling glycogen metabolism, glycolysis, gluconeogenesis, fatty acid synthesis, cholesterol synthesis, and protein synthesis are reviewed.
Abstract: Protein phosphorylation is a principal regulatory mechanism in the control of almost all cellular processes. The nature of the protein phosphatases that participate in these reactions has been a subject of controversy. Four enzymes, termed protein phosphatases 1, 2A, 2B, and 2C, account for virtually all of the phosphatase activity toward phosphoproteins involved in controlling glycogen metabolism, glycolysis, gluconeogenesis, fatty acid synthesis, cholesterol synthesis, and protein synthesis. The properties, physiological roles, and mechanisms for regulating the four protein phosphatases are reviewed.

631 citations


Journal ArticleDOI
TL;DR: Four members of a Gardner's syndrome family had rectal and colon polyposis treated with nonsteroid anti‐inflammatory drugs and the residual polyps arose in the rectal mucosa and almost completely disappeared when sulindac was administered.
Abstract: Four members of a Gardner's syndrome family had rectal and colon polyposis treated with nonsteroid anti-inflammatory drugs. Three of these patients had had subtotal colectomy and ileoproctostomy and the residual polyps arose in the rectal mucosa. The polyps almost completely disappeared when sulindac was administered. Indomethacin therapy over the course of a preceding year was ineffective in one of these patients. One patient (case 4) had diffuse polyposis in an intact colon. After sulindac therapy for a year, only three small mucosal polyps could be identified by air contrast barium enema and colonoscopic examination. These observations confirm those of Pollard and Luckert [1,2] on rats with chemically induced polyposis of the intestinal tract.

562 citations


Journal ArticleDOI
TL;DR: This work proposes preliminary diagnostic criteria for EM, based primarily on clinical features, and suggests that recurrent herpes simplex is an important etiologic factor in EM minor, while mycoplasmal infections and drugs may be associated with EM major.
Abstract: Erythema multiforme (EM), in its modern definition, is an acute, self-limited syndrome with distinctive skin lesions with or without mucosal lesions. Use of the terminology "EM minor" and "EM major" is a reasonable approach to separating the classical mild cutaneous syndrome, as described by Hebra (EM minor), from the usually more severe syndrome, with marked mucosal damage, as described by Stevens and Johnson (EM major). Until objective markers for EM are available, we propose preliminary diagnostic criteria for EM, based primarily on clinical features. Although hundreds of factors have been reported to cause EM, only a limited number are reasonably well documented as possible precipitating agents. Recurrent herpes simplex is an important etiologic factor in EM minor, while mycoplasmal infections and drugs may be associated with EM major. Progress in the understanding of EM will require careful attention to definition and diagnostic criteria and identification of distinct clinical and etiologic subsets within the spectrum of EM.

445 citations


Book ChapterDOI
TL;DR: Urogenital mesenchyme induces specific epithelial morphogenesis, growth, and function within the genital tract and that the hormonal sensitivity of these morphogenetic processes resides in the mesenchYme that invariably contains nuclear hormone receptors.
Abstract: Publisher Summary This chapter explains the role of mesenchymal–epithelial interactions in hormone induced morphogenesis and growth. The mechanism of steroid hormone action is thought to involve specific high-affinity receptor proteins. The hormone enters the cell, binds to the cytoplasmic receptor, which after activation translocates to the nucleus. The hormone–receptor complex in turn binds to nuclear acceptor sites on the chromatin. This activates a variety of metabolic processes, the most important being the stimulation of messenger RNA (mRNA) synthesis and the ultimate production of new proteins. The first indication that androgens can elicit their effects upon epithelial morphogenesis via the mediation of mesenchymal cells comes from studies in which urogenital epithelia from the embryonic seminal vesicle or urogenital sinus are grown in association with either urogenital mesenchyme or with non-target integumental mesenchyme. Urogenital mesenchyme induces specific epithelial morphogenesis, growth, and function within the genital tract and that the hormonal sensitivity of these morphogenetic processes resides in the mesenchyme that invariably contains nuclear hormone receptors. As morphogenetic processes are cyclic in adult genital tracts of many species, developmental properties are expressed in adulthood and, for this reason, appear to play a regulatory role in abnormal epithelial differentiation including carcinogenesis.

436 citations


Journal ArticleDOI
18 Mar 1983-Science
TL;DR: Results from linkage analysis in families with apparent autosomal dominant reading disability strongly suggest that a gene playing a major etiologic role in one form of reading disability is on chromosome 15.
Abstract: Linkage analysis in families with apparent autosomal dominant reading disability produced a lod score of 3.241. Since the traditionally accepted significance level for linkage is a lod score of 3.0, these results strongly suggest that a gene playing a major etiologic role in one form of reading disability is on chromosome 15.

335 citations


Journal ArticleDOI
TL;DR: The findings indicate that the primary biochemical defect in late-onset multiple carboxylase deficiency is in biotinidase activity which is inherited as an autosomal recessive trait.

293 citations


Journal ArticleDOI
TL;DR: It is concluded that prolonged oxygen treatment is associated with small but definite improvement in brain functioning among patients with hypoxemic COPD, and that COT might have some advantage over NOT in enhancing neuropsychologic functioning as well as survival.
Abstract: • The Nocturnal Oxygen Therapy Trial (NOTT) showed previously that patients with hypoxemic chronic obstructive pulmonary disease (COPD) frequently suffered from neuropsychologic deficit and experienced disturbed mood, personality, and life quality. The present study has followed up 150 NOTT patients six months after they were randomized to continuous oxygen treatment (COT) or nocturnal oxygen treatment (NOT). Tested off oxygen, 42% showed modest neuropsychologic improvement after six months of therapy, and the rates for COT and NOT were comparable. A subsample (n = 37) was examined a third time, after 12 months of treatment. At this point patients receiving COT registered better neuropsychologic performance than those receiving NOT. Concurrently, the COT group began showing improved survival. Despite mild neuropsychologic improvement, patients reported little change in emotional status or life quality. It is concluded that prolonged oxygen treatment is associated with small but definite improvement in brain functioning among patients with hypoxemic COPD, and that COT might have some advantage over NOT in enhancing neuropsychologic functioning as well as survival. (Arch Intern Med1983;143:1941-1947)

270 citations


Journal ArticleDOI
TL;DR: The denatured peptide displayed an electrophoretic microheterogeneity which may be ascribed to variations in bulky carbohydrate substituents and an extremely high free mobility which is inferred to result from binding of unusually large amounts of NaDodSO4.
Abstract: Preparations of the tetrodotoxin (TTX) and saxitoxin binding protein isolated from the electroplax of Electrophorus electricus are of high specific activity (greater than or equal to 2000 pmol of TTX binding sites/mg of protein) and appear to be homogeneous in that they contain only the large polypeptide previously identified to make up part of the voltage-sensitive sodium channel [Agnew, W. S., Moore, A. C., Levinson, S. R., & Raftery, M. S. (1980) Biochem. Biophys. Res. Commun. 92, 860-866]. This permits the inference that the TTX binding site, thought to be associated with the mouth of the ion channel, is located on this peptide. This peptide presumably corresponds to the large peptide, designated the alpha-peptide subunit, of the synaptosomal sodium channel [Hartshorne, R. P., & Catterall, W. A. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 4620-4624]. No convincing evidence for lower molecular weight peptides has yet been found for the electroplax protein. A rapid and convenient method is described for preparation of milligram quantities of the pure, sodium dodecyl sulfate (NaDodSO4) denatured form of the peptide, and its amino acid and carbohydrate compositions are reported. The peptide behaved anomalously on NaDodSO4-polyacrylamide gels. It was demonstrated that the molecular weight cannot be accurately quantified by this method but that the true value likely exceeds the value of 260 000 reported previously. The denatured peptide displayed an electrophoretic microheterogeneity which may be ascribed to variations in bulky carbohydrate substituents and an extremely high free mobility which is inferred to result from binding of unusually large amounts of NaDodSO4.

242 citations


Journal ArticleDOI
TL;DR: It is suggested that augmentation of GABA effects is involved in the incoordinating and soporific actions of ethanol, and one factor responsible for genetic differences in ethanol response is sensitivity to GABA; and ethanol tolerance and dependence may be related to decreased sensitivity toGABA.

213 citations


Journal ArticleDOI
TL;DR: The use of smokeless tobacco appears to be finding its way onto middle school, high school and college campuses as a socially acceptable and popular habit and a combination of oral mucosal lesions and periodontal inflammation, and cervical erosion of the teeth.

175 citations


Journal ArticleDOI
27 May 1983-Science
TL;DR: Brain poly(A)- mRNA's specify proteins required for the biological capabilities of the brain that emerge during the course of postnatal development, suggesting that the full adult complement is not reached until young adulthood.
Abstract: The adult mouse brain contains complex populations of polyadenylated [poly(A)+] and nonpolyadenylated [poly(A)-] messenger RNA's (mRNA's). These mRNA's are separate sequence populations, similar in complexity, and in combination are equivalent to approximately 150,000 different mRNA sequences, of average length. Essentially all of the "adult" poly(A)+ mRNA's are present in the brain at birth. In contrast, most of the poly(A)- mRNA's are absent. Brain poly(A)- mRNA's begin to appear soon after birth, but the full adult complement is not reached until young adulthood. This suggests that these poly(A)- mRNA's specify proteins required for the biological capabilities of the brain that emerge during the course of postnatal development.

Journal ArticleDOI
TL;DR: Outpatient mental health treatment can be included in a fee-for-service medical care system to improve the quality and appropriateness of care and, if not extensive, may also serve to lower medical care costs.
Abstract: Charges for medical services of persons covered by the Blue Cross/Blue Shield Federal Employees Program from 1974 through 1978 who were first diagnosed as having one of four chronic diseases in 1975 and within one year began mental health treatment (MHT) were compared with persons who also were first diagnosed as having one of these diseases in 1975 but had no subsequent MHT. In the third year following the diagnosis, those having seven to 20 MHT visits had medical charges $309 lower and those having over 21 MHT visits had medical charges $284 lower than the comparison group. The savings in medical charges over three years of the group having seven to 20 MHT visits were a function of lower use of inpatient services and roughly equaled the cost of 20 MHT visits. Outpatient mental health treatment can be included in a fee-for-service medical care system to improve the quality and appropriateness of care and, if not extensive, may also serve to lower medical care costs.

Journal ArticleDOI
TL;DR: It is concluded that during sleep the presence of acid in the lower esophagus can trigger bronchoconstriction in asthmatic children with a positive Bernstein test and that these children appear to be more susceptible to the bronchconstrictive effects of intraesophageal acid at 4 to 5 A.M. than at midnight.
Abstract: Nocturnal asthma has been associated with nighttime gastroesophageal reflux (GER). To establish whether the presence of acid in the lower esophagus causes bronchoconstriction, nine children with nocturnal asthma and GER underwent intraesophageal acid-infusion challenges during sleep. The patients were divided into two groups on the basis of presence or absence of a positive Bernstein test for esophagitis. The test was considered positive if acid infusion produced symptoms of heartburn. On two occasions, at approximately midnight and 4 to 5 a.m., 30 ml of normal saline was infused over 15 min into the distal esophagus followed by a similar infusion of 0.1N HCl. Respiration was continuously monitored by inductance plethysmography along with clinical evaluation. The saline and midnight acid infusions had no effect in either patient group; however, with the 4 to 5 a.m. acid infusion, all the patients with a positive Bernstein test developed significant changes in their respiratory pattern indicative of bronchoconstriction as well as overt clinical wheezing. In the patients with a negative Bernstein test, the 4 to 5 a.m. acid infusion had no effect. It is concluded that during sleep the presence of acid in the lower esophagus can trigger bronchoconstriction in asthmatic children with a positive Bernstein test and that these children appear to be more susceptible to the bronchoconstrictive effects of intraesophageal acid at 4 to 5 a.m. than at midnight.

Journal ArticleDOI
TL;DR: It is proposed that the rapid rise in the serum sodium level causes an osmotic injury to the endothelium resulting in the release of myelinotoxic factors and/or the production of vasogenic edema, which may lead to demyelination.
Abstract: Central pontine myelinolysis (CPM) is a demyelinative disorder of unknown origin. Recent clinical and experimental studies have indicated an association of CPM with a rise in the serum sodium level. I propose that the rapid rise in the serum sodium level causes an osmotic injury to the endothelium resulting in the release of myelinotoxic factors and/or the production of vasogenic edema. The latter factors may lead to demyelination. The patient at risk, viz, a chronically ill, alcoholic, cirrhotic person, may be the one least able to generate protective cerebral mechanisms against the osmotic stress. The location of lesions may be explained by a suitable anatomic arrangement consisting of an extensive admixture of gray and white matter; thus, myelinotoxic factors derived from the richly vascular gray are able to interact with adjacent bundles of myelin-containing white matter.

Journal ArticleDOI
TL;DR: It is proposed that congenital heart block may be related to transplacental passage of maternal SS-A/Ro antibodies and that neonatal lupus may be the most common cause.

Book ChapterDOI
01 Jan 1983
TL;DR: The location and external form of the mammary gland differ from one species to another, the mechanisms of milk production are remarkably similar, and these structures may provide additional milk storage, particularly in dairy animals.
Abstract: Milk secretion occurs in all mammals, the presence of mammary glands being one of the important criteria distinguishing this class from all others. Although the location and external form of the mammary gland differ from one species to another, the mechanisms of milk production are remarkably similar. Milk is produced by epithelial cells which line the mammary alveoli and is stored in the alveolar lumina adjacent to these cells. During ejection, the milk is forced from the alveoli by contraction of surrounding myoepithelial cells and exits through ductules into ducts which drain several clusters of alveoli. In the human, small ducts coalesce into 15 to 25 larger ducts which dilate into small sinuses as they near the areolus. These ducts open directly on the nipple (see Chapter 2 for a more extensive discussion of the anatomy of the human mammary gland). In other animals, the ducts may empty into a single primary duct or a cistern which in turn is drained by a single teat canal. These structures may provide additional milk storage, particularly in dairy animals.

Journal ArticleDOI
01 Sep 1983-Peptides
TL;DR: The N-terminal heptapeptide fragment of SP, SP(1-7), inhibits nociceptive, aggressive and grooming behaviors and stimulates investigative motor behavior, but the C- terminal hexapeptides fragment analog pyroglutamyl-SP(7-11) exerts opposite effects.

Journal ArticleDOI
TL;DR: Six patients with the fragile X syndrome are autistic and demonstrate similar profiles on three evaluations designed to measure the severity of autism.
Abstract: Ten patients with the fragile X syndrome were diagnosed at the Child Development Unit in 1982. Six of these patients are autistic and demonstrate similar profiles on three evaluations designed to measure the severity of autism. The similarities of these six autistic patients are described in depth.

Journal ArticleDOI
TL;DR: Oxidation fractions and rates for both glucose and lactate increased with their concentrations in fetal blood suggesting sparing of other fuels for oxidation at higher glucose and dairy concentrations.
Abstract: Both glucose and lactate are nutrients of the ovine fetus. Each may be used by the fetus as a fuel for oxidation or as a source of carbon for energy storage and net tissue accretion. The present report describes the oxidation rates of glucose and lactate in vivo for the fetal lamb over a relatively short time period. The fraction of fetal glucose or lactate oxidized was defined as the ratio of 14CO2 excretion across the umbilical circulation to the net entry of [14C]glucose or [14C]lactate into fetal tissues. The fraction of glucose oxidized over a 3-hr study averaged 61.2%, accounting for 2.55 mg X min-1 X kg-1 of glucose oxidized and for 28% of the simultaneous net oxygen uptake. The fraction of lactate oxidized averaged 71.5%, accounting for 4.12 mg X min-1 X kg-1 of lactate oxidized. Oxidation fractions and rates for both glucose and lactate increased with their concentrations in fetal blood suggesting sparing of other fuels for oxidation at higher glucose and lactate concentrations.

Journal ArticleDOI
TL;DR: The results indicated that epinephrine 1/200,000 reduces vascular absorption of epidural morphine and intensifies all the manifestations of cord and brainstem uptake.
Abstract: The effects of epinephrine 1/200,000 as an adjuvant to epidural morphine were investigated in three healthy male volunteers, during 26-h observation sessions. Peak blood concentrations of morphine were 44 +/- 12.9 ng/ml after plain morphine and 13.7 +/- 6.7 ng/ml after epinephrine-morphine. Cutaneous hypalgesia was more intense, faster in onset, and longer in duration after epinephrine-morphine than after plain morphine, and analgesia to ice-water immersion of extremities lasted longer. Adverse side effects of pruritus, nausea, vomiting, and difficulty of micturition were also more intense after epinephrine-morphine, and respiratory sensitivity to CO2 was depressed more severely between 6 and 16 h. The results indicated that epinephrine 1/200,000 reduces vascular absorption of epidural morphine and intensifies all the manifestations of cord and brainstem uptake.

Journal ArticleDOI
TL;DR: Fecal and ileal cultures showed that C. jejuni and related organisms are not bowel commensals, and this model may be useful for evaluating the effects of prophylactic and therapeutic interventions.
Abstract: HA-ICR adult mice were studied to develop an animal model for Campylobacter jejuni enteritis in humans. Fecal and ileal cultures made by selective and nonselective methods showed that C. jejuni and related organisms are not bowel commensals. Intragastric feeding of 108 CFU of three different strains of C. jejuni produced infection in 100% of the animals, and infection rates were dose dependent. Pretreatment with antibiotics or opiates was not necessary to induce infection. Fresh isolates and strains passed on artificial media yielded similar infection rates. Infected mice did not show signs of illness, but transient bacteremia within 10 min of oral infection was observed in nearly 100%. The small intestine was the principal target organ, with epithelial inflammation seen 48 h after infection. Control mice of four species had undetectable serum immunoglobulin G antibody specific for the infecting strain, but infected mice showed peak titers at 1 week with rapid decline. Immunoglobulin M titers rose minimally, and immunoglobulin A titers did not rise. Infected mice uniformly became chronic asymptomatic excretors, shedding 104 to 106 CFU/g of feces; a minority were biliary carriers. Intestine carriage was most pronounced in the stomach and proximal small intestine. Because this experimental infection led to bacteremia, transient pathological changes, and immunoglobulin G titer rises, this model may be useful for evaluating the effects of prophylactic and therapeutic interventions. Images

Journal ArticleDOI
TL;DR: In this group of animals the mineral apposition rate was reduced at the metaphyseal endosteum but increased at the periosteUM, indicating different control mechanisms at the two sites, and aluminum administration caused no skeletal changes in nonuremic animals.
Abstract: The effects of intraperitoneal aluminum chloride (1.5 mg aluminum/kg/day for 9 weeks) were studied in normal and uremic rats. Parameters measured included tissue aluminum, serum vitamin D metabolites, and quantitative bone histology.

Journal ArticleDOI
TL;DR: Fibronectin may be part of a provisional matrix that functions to support, if not actively participate in, cell recruitment to sites of inflammation or wound healing.

Journal ArticleDOI
TL;DR: Overall rates of febrile respiratory diseases have been greatly reduced and Adenovirus disease has been virtually eliminated since live oral types 4 and 7 vaccines have been given to incoming recruits.
Abstract: Surveillance of febrile respiratory diseases at Lowry Air Force Base, Denver, has been maintained from 1952 to 1982 with laboratory confirmation of diagnosis. Unvaccinated recruit populations were extremely vulnerable to explosive outbreaks of influenza A. Ten controlled trials demonstrated the protective efficacy of inactivated vaccines. Recent military vaccines have raised the hemagglutination-inhibiting antibody levels of most persons into the "protective" range. Despite repeated introduction of influenza viruses onto the base, when all personnel were vaccinated the impact of influenza was reduced to an insignificant level except in one year of antigenic shift (1968) and one of major antigenic drift (1972). Adenovirus disease has been virtually eliminated since live oral types 4 and 7 vaccines have been given to incoming recruits. Rubella and rubeola have disappeared since seronegative recruits have received vaccine. Overall rates of febrile respiratory diseases have been greatly reduced. In the 1950s Lowry Air Force Base in Denver, from the standpoint of acute febrile upper respiratory disease, had the well-deserved reputation of being an unhealthy place. Explosive influenza epidemics occurred at frequent intervals. Epidemics of acute viral pharyngitis, later shown to be caused by adenoviruses, affected major segments of the recruit population. Streptococcal disease was rampant, and up to 120 cases of acute rheumatic fever


Journal ArticleDOI
TL;DR: The fractional distribution of maternally produced glucose among nonuterine maternal tissues, the fetus, and the uteroplacenta was not altered markedly by hypoglycemia despite a 57% reduction in maternal glucose production.
Abstract: Experiments were conducted in late-gestation, conscious, pregnant ewes to measure maternal glucose production and the net glucose uptake by the uterus, fetus, uteroplacenta, and nonuterine maternal tissues. Glucose concentration in the ewes varied naturally or decreased in response to fasting. Normoglycemic ewes (63.8 +/- 8.7 mg/dl) had a glucose production rate of 178.7 +/- 44.5 mg/min compared with a rate of 76.9 +/- 20.6 mg/min for hypoglycemic ewes (34.7 +/- 7.4 mg/dl). Uterine glucose uptake (56.5 +/- 16.8 mg/min), fetal glucose uptake (15.7 +/- 5.2 mg/min), uteroplacental glucose uptake (40.8 +/- 13.4 mg/min), and nonuterine maternal glucose uptake (122.2 +/- 27.7 mg/min) in the normoglycemic ewes were significantly greater than in the hypoglycemic ewes (28.7 +/- 5.4, 7.5 +/- 4.4, 21.2 +/- 6.6, and 48.2 +/- 15.2 mg/min, respectively). The fractional distribution of maternally produced glucose among nonuterine maternal tissues, the fetus, and the uteroplacenta was not altered markedly by hypoglycemia despite a 57% reduction in maternal glucose production.

Journal ArticleDOI
TL;DR: The BESC provides one way to describe how patients cope with and experience chronic bronchitis and emphysema and the relationships among categories are stable across two subgroups of patients.
Abstract: Subjective symptoms and experiences were explored within a group of 146 severe, chronic bronchitis and emphysema patients. Eighty-nine symptoms and experiences, derived from initial interviews with 29 patients, were rated according to the frequency of occurrence during breathing difficulties. Key cluster analyses were used to derive a Bronchitis-Emphysema Symptom Checklist (BESC) measuring 11 symptom categories: Helplessness-Hopelessness, Decathexis, Fatigue, Poor Memory, Peripheral-Sensory Complaints, Dyspnea, Congestion, Sleep Difficulties, Irritability, Anxiety, and Alienation. The BESC symptom categories are highly reliable and the relationships among categories are stable across two subgroups of patients. The BESC provides one way to describe how patients cope with and experience chronic bronchitis and emphysema.

Journal ArticleDOI
TL;DR: Before it is possible to protect children and to develop therapeutic services for the family, it will be necessary to acknowledge that sexual abuse is part of the child abuse spectrum.

Journal ArticleDOI
TL;DR: Eight patients with alcoholic liver disease, ascites, and edema were found to have impaired water and sodium excretion during a 20 ml/kg water load and a significant positive correlation was found between the increase in fractional excretion of sodium (delta FENa) and the increased in RAP.

Journal ArticleDOI
TL;DR: In this article, a study of four hundred and thirty-three managerial dyads were studied in order to test aspects of Graen's role-making model of leadership and found that negotiating latitude was positively related to job satisfaction and negatively related to their job problems, but to be uncorrelated with numbers of hours spent working.
Abstract: Four hundred and thirty-three managerial dyads were studied in order to test aspects of Graen's role-making model of leadership. Subordinates' negotiating latitude was found to be positively related to their job satisfaction and negatively related to their job problems, but to be uncorrelated with numbers of hours spent working. Leaders' negotiating latitude was not significantly associated with rated effectiveness of subordinates. Other predictions from the model were also unsupported. Conceptual and methodological suggestions for future research are offered.