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Biomedical subjects

R A Johnson

Publications and source records attributed to R A Johnson.

At least 163 records · Page 9Linked to original sources
PubMed1990

Appropriate public health responses to clusters: the art of being responsibly responsive.

Between 1981 and 1988, the Minnesota Department of Health actively responded to over 400 reports from persons concerned about disease occurrence in their community, school, or workplace. Almost all of these reports involved perceived excesses of cases of cancer. Although there is little potential for identifying unsuspected public health problems or developing new etiologic insights, the Minnesota Department of Health has found that responding to reported clusters is a legitimate and necessary public health activity. To be responsibly responsive to these concerns, the Department has developed four steps to prioritize investigation of reported disease clusters, as well as six criteria for determination of the feasibility of environmental epidemiologic investigations. Approximately 95% of all concerns have been handled within the first two steps of this approach, generally requiring only education, or sometimes examination of readily-available data. Less than 5% of the concerns have required additional data collection and evaluation, and only about 1% have resulted in full-scale epidemiologic studies. Successful conclusions at all levels of this process require that public health officials develop effective communication, maintain objectivity, and provide leadership for controversial and difficult issues.

Clinical Protocols↗
PubMed1990

Pain on injection of propofol. Methods of alleviation.

A controlled randomised double-blind design was used to study the effect of lignocaine on the pain produced by intravenous injection of propofol. Patients received a 2-ml pretreatment solution with temporary venous occlusion, followed by an induction solution. One hundred and three patients were assigned to one of five groups: saline pretreatment, followed by induction with propofol plus saline 2 ml; lignocaine 20 mg pretreatment, followed by induction with propofol plus saline 2 ml; lignocaine 40 mg pretreatment, followed by induction with propofol plus saline 2 ml; saline pretreatment, followed by induction with propofol plus lignocaine 20 mg; or saline pretreatment, followed by induction with propofol plus lignocaine 40 mg. Pain was reduced significantly in all groups in which lignocaine was used and a dose of 40 mg was more effective than 20 mg. There were no significant differences in the incidence of pain among the groups which received lignocaine as pretreatment and the groups which received lignocaine mixed with propofol. Sixty-eight percent of patients who experienced pain or discomfort recalled it in the postoperative period.

Double-Blind Method↗
PubMed1990

Creative thinking in mentally retarded deaf adolescents.

30 mentally retarded deaf adolescents were matched with 30 mentally retarded hearing adolescents to evaluate (a) differences in creative thinking as a function of hearing status, (b) the effect of severity of mental retardation on hearing status, and (c) interaction between hearing status and intelligence. A multivariate factorial analysis of variance indicated that the mentally retarded deaf adolescents differed significantly from hearing adolescents on Fluency and Originality. The deaf youth scored higher on Fluency while the hearing scored higher on Originality. No other effects in the analysis reached significance.

Adolescent↗
PubMed1990

Protein kinase C activators sensitize cyclic AMP accumulation by intact 1321N1 human astrocytoma cells.

Pretreatment of 1321N1 human astrocytoma cells with phorbol 12-myristate-13-acetate or other activators of protein kinase C led to 2.5- to 5-fold increases (sensitization) in subsequent stimulation by forskolin of intracellular cyclic AMP accumulation. These compounds caused much smaller or no increases in receptor-mediated stimulation of cyclic AMP accumulation induced by isoproterenol and by prostaglandin E1. Carbachol and histamine, agonists acting at receptors coupled to polyphosphoinositide turnover in these cells, induced less sensitization of subsequent stimulation by forskolin but greater sensitization of stimulation by isoproterenol and by prostaglandin E1. The specificities of various analogs of phorbol 12-myristate-13-acetate, for induction of sensitization of forskolin stimulation were consistent with involvement of protein kinase C. The effects of protein kinase inhibitors and of down-regulation of protein kinase C activity also indicated involvement of protein kinase C in sensitization of forskolin stimulation, although additional mechanisms are likely to be involved in sensitization of isoproterenol stimulation. Neither pertussis toxin pretreatment nor inclusion of isobutylmethylxanthine during assays of cyclic AMP accumulation were able to prevent or mimic these sensitization phenomena, suggesting that the primary site of modification responsible for sensitization is neither the inhibitory guanine nucleotide-binding protein nor cyclic AMP phosphodiesterase. Sensitization was only observed in assays with intact cells. These results, together with those from our previous study describing protein kinase C-mediated desensitization of broken cell adenylate cyclase activity, indicate that activation of protein kinase C leads to multiple changes in the receptor-stimulated adenylate cyclase signal transduction pathway of these cells.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Tissue levels, source, and regulation of 3'-AMP: an intracellular inhibitor of adenylyl cyclases.

Tissue levels of 3'-AMP were measured in several rat tissues and the sensitivities of the respective adenylyl cyclases were compared with respect to "P" site-mediated inhibition by 3'-AMP2'-deoxy-3'AMP (2'd3'-AMP), and 2',5'-dideoxyadenosine. IC50 values for these P site inhibitors of adenylyl cyclases varied widely among tissues, e.g., with skeletal muscle being least sensitive to 3'-AMP (IC50 greater than 170 microM) and brain being most sensitive (IC50 approximately 10 microM). These differences were noted when activation was with Mn2+ but diminished with Mn2+ plus forskolin and conceivably may reflect the distribution of different isozymes of adenylyl cyclase. 3'-AMP levels also varied significantly among rat tissues, with spleen having the highest levels (approximately 280 nmol/g), kidney, liver, heart, and brain having decreasing 3'-AMP content, and skeletal muscle levels being immeasureably low (less than 0.1 nmol/g). When rats were made diabetic with streptozotocin, the 3'-AMP content of livers increased from approximately 47 nmol/g in control animals to approximately 84 nmol/g, a change largely reversed by maintenance of diabetic animals with insulin. The data suggest that tissue 3'-AMP levels may be regulated and in certain tissues may be sufficient to inhibit adenylyl cyclase in vivo. Three potential sources of 3'-AMP and 2'd3'-AMP, the most potent naturally occurring P site inhibitors of adenylyl cyclase, were examined. No evidence was found for the formation of either nucleotide from the respective cyclic nucleotide by a unique cyclic nucleotide phosphodiesterase or from the respective nucleoside by a hypothetical adenosine 3'-kinase and ATP. Substantial 3'-AMP and 2'd3-AMP were formed by spleen and liver homogenates from the respective oligonucleotides (RNA, mRNA, and DNA) in a time- and protein-dependent manner. The data imply the existence of enzymes in these tissues to catalyze the formation of 3'-AMP and 2'd3'-AMP from nucleic acids and suggest that these activities may account for the formation of P site agonists under in vivo conditions. The data suggest that these P site inhibitors are a potential link between fluctuations in nucleic acid metabolism and altered sensitivity of membrane-bound adenylyl cyclase to stimulatory signals.

Adenosine Monophosphate↗
PubMed1990

Controlled evaluation of implementing the Cytobrush technique to improve Papanicolaou smear quality.

The effect of introducing the Cytobrush Cell Collector for endocervical sampling on the quality of Papanicolaou smears was evaluated using a quasi-experimental design. Baseline evaluation of the Ayre spatula-cotton swab method in two patient groups showed that only 61.8-61.9% of smears contained endocervical cells. Replacing the cotton swab with the Cytobrush in the intervention group improved endocervical cell yields to 82.0% (P less than .001). This improvement was not due to group differences in patient factors previously related to endocervical cell yields, eg, parity, use of oral contraceptives, pregnancy, previous cervical procedures, and menopausal status. An increase in the proportion of Papanicolaou smears showing dysplasia or cancer (class III or higher) was associated with use of the Cytobrush (P less than .05). Subsequent introduction of the Cytobrush to the control group resulted in a similar significant improvement in cell yields to 82.5% (P less than .001). Greater use of methods such as the Cytobrush Cell Collector in the primary care setting can improve cervical cancer screening by reducing the number of false-negative Papanicolaou smears resulting from inadequate endocervical cell sampling.

Adult↗
PubMed1990

Lymphoscintigraphy and lymphedema of the lower extremities.

Lymphoscintigraphy, using technetium-99m-labeled sulphur microcolloid, was employed to study the flow and transport of lymph in the lower extremities of 39 consecutive patients in whom lymphedema of one or both legs was suspected clinically. Time-activity curves of four segments of each leg were evaluated for lymph capacity, flow and soft-tissue uptake, and compared with the results from film scintigraphy. Curve analysis provided quantitative evaluation of the extent of hypoplasia or aplasia in primary lymphedema and of lymphatic obstruction in secondary lymphedema, and is particularly suited to assess the involvement of lymphatics in chronic venous disease. Film scintigraphy, on the other hand, is preferable in cases in which the pattern of activity distribution in the affected extremity is diagnostic, such as in dermal back flow, traumatic lymphocele, or megalymphatics. Venography is most informative in cases of suspected underlying venous disease, but the role of lymphangiography, which shows only part of the lymphatic system and requires incision of the edematous tissues, is considered questionable.

Adult↗
PubMed1989

Forskolin decreases sensitivity of brain adenylate cyclase to inhibition by 2',5'-dideoxyadenosine.

The effects of forskolin on the sensitivity of adenylate cyclase to 'P'-site-mediated inhibition were studied. Stimulation of crude and purified preparations of adenylate cyclase by forskolin led to decreased sensitivity to inhibition by 2',5' dideoxyadenosine with enzyme from rat and bovine brain. This is in contrast with the enhancement of P-site sensitivity induced by calmodulin, divalent cations, and stable GTP analogs and is in contrast with behavior seen with enzyme from liver and S49 cyc membranes. The effect of forskolin on P-site sensitivity of the brain adenylate cyclase was not dependent on the presence of G-proteins or calmodulin. It was not the consequence of proteolysis nor was it due to an obvious artifact in the assay procedures. This distinct behavior of the brain enzyme is most likely due to a structural difference in the catalytic subunit.

Adenylyl Cyclase Inhibitors↗
PubMed1989

Minnesota highway maintenance worker cohort mortality study: methods and noncancer mortality.

In 1984, the Minnesota Department of Health (MDH) began a cohort mortality study of 4,849 workers to follow up concerns with the health and safety of highway maintenance workers (HMWs). A total of 1,530 deaths had occurred, resulting in a standardized mortality ratio (SMR) of 91 (p less than .01) and an all cancer SMR of 84 (p less than .01). There was a significant elevation in the SMR for chronic renal failure among long-term rural workers (SMR = 676, p less than .05). The SMR was also elevated for transportation injuries. The latter SMR was highest among short-term urban workers (SMR = 280, p less than .01). In addition, the SMR for transportation-related injury deaths tended to increase the later the decade of starting work. The SMRs were 137, 259, 502, and 2,145 for urban workers starting work in the decades 1945-1954, 1955-1964, 1965-1974, and 1975-1984, respectively. This study demonstrates the possible adverse health effects of highway maintenance work and the need to comprehensively evaluate injury mortality among selected occupational cohorts.

Accidents, Traffic↗
PubMed1989

Minnesota Highway Maintenance Worker Study: cancer mortality.

Highway maintenance workers (HMWs) have been exposed to a broad range of potentially toxic substances, including diesel fuels and exhaust, asphalts and tars, herbicides, gasoline, polynuclear aromatic hydrocarbons, benzene, and lead. The number of current and former state, county, and municipal HMWs in the United States exceeds 500,000, yet the health risks of this occupation had never been studied. To fill this void and to respond to the public perception that Minnesota HMWs were at high risk of developing leukemia, an occupational cohort mortality study was conducted of Minnesota HMWs employed between 1945 and 1984. Leukemia mortality in HMWs with 30-39 years of work (standardized mortality ratio [SMR] = 425; 95% confidence interval [CI] = 171-876) and urologic cancer mortality in HMWs with 40-49 year latency (SMR = 292; CI = 117-602) were significantly elevated. The extent to which these and other findings were directly related to work exposures is unknown. Further investigations to resolve the significance of the risks associated with the HMW occupation are currently underway.

Cohort Studies↗
PubMed1989

Tumor necrosis factor alpha and the anemia of chronic disease: effects of chronic exposure to TNF on erythropoiesis in vivo.

The anemia of chronic disease is associated with conditions in which macrophage activation occurs. Activated marrow macrophages suppress erythropoiesis in vitro, and produce tumor necrosis factor (TNF). Therefore, we tested the effects of chronic in vivo exposure to TNF to determine if it were a candidate for a mediator of the anemia of chronic disease. Nude mice were inoculated with CHO cells expressing the human TNF gene, or with control cells containing the transfection vector alone. The TNF mice promptly became reticulocytopenic, and after 3 weeks their corrected reticulocytes were 2.6 +/- .7% compared to 7.3 +/- 4% in control mice. The hematocrit at 3 weeks was 28.4 +/- 1.7% in TNF mice compared to 46 +/- 8% in control mice. This anemia was also associated with low serum iron and normal iron stores and increased erythropoietin levels. The TNF mice showed an absolute monocytosis with twice the number of circulating monocytes as control mice. The TNF mice also became mildly thrombocytopenic. Marrow CFU-E and BFU-E were profoundly decreased (1.2 +/- 2 x 10(3) vs 8.6 +/- 2 x 10(4) CFU-E per femur, and 6.5 +/- 1 x 10(2) vs 8.5 +/- .2 x 10(4) BFU-E per femur). Splenic CFU-E and BFU-E were similarly depressed. In contrast, marrow CFU-GM and CFU-GEMM were not affected. Administration of recombinant human erythropoietin to these mice failed to reverse the suppressed erythropoiesis in mice bearing TNF producing tumors. These data demonstrated that TNF preferentially inhibits erythropoiesis in vivo, and may be important in the pathogenesis of the anemia of chronic disease.

Anemia↗
PubMed1989

Ammonium ions enhance proteolytic activation of adenylate cyclase and decrease its sensitivity to inhibition by "P"-site agonists.

A detergent-dispersed adenylate cyclase from rat brain was used to study the effects of ammonium salts and polyamines on the proteolytic activation of the enzyme by a sperm protease and on the sensitivity of adenylate cyclase to inhibition via its "P"-site. A purified preparation of a trypsin-like, serine protease from bovine sperm was used to activate solubilized adenylate cyclase in the presence of guanosine 5'-O-(3-thiotriphosphate (GTP gamma S). The proteolytically activated form of adenylate cyclase was found to be particularly sensitive to further activation by ammonium bicarbonate. The activation by NH4HCO3 was found to be due to the NH+4 cation and was characterized by an increased Vmax and by a decreased sensitivity of adenylate cyclase to inactivation by elevated concentrations of the sperm protease or by trypsin. NH4Cl and (NH4)2SO4 also caused biphasic effects on adenylate cyclase, which mimicked but were less effective than those caused by NH4HCO3. Consistent with observations of others, adenylate cyclase activity was enhanced by ammonium ions whether in the presence of reversible (Mn2+) or irreversible (GTP gamma S) activators. Mn2+- and GTP gamma S-stimulated activities were similarly optimally enhanced by 30 mM (NH4)2SO4 and by 30 to 150 mM NH4Cl or NH4HCO3. Ammonium ions did not increase the activity of the purified catalytic unit. Moreover, the effect of ammonium ions was not accompanied by an increased rate of activation by GTP gamma S, suggesting that the activation of Gs (guanine nucleotide-dependent stimulatory component) may not be the primary cause of stimulation by ammonium salts. Several polyamines at millimolar concentrations blocked the stimulatory effect of NH+4. This was observed when adenylate cyclase was activated by Mn2+, but not when it was activated by GTP gamma S or by the sperm protease + GTP gamma S. The inhibitory effect of polyamines was not due to the formation of a complex with ATP. Both the increase in Vmax of the Mn2+-stimulated enzyme by NH+4 and the decrease in Vmax caused by spermine were accompanied by an increase in the enzyme's Km MnATP app. Spermine increased the IC50 for inhibition of Mn2+-activated adenylate cyclase by 2',5'-dideoxyadenosine (2',5'-ddAdo) from 0.75 to 4.6 microM, consistent with the idea that increased sensitivity of P-site-mediated inhibition is associated with increased enzyme activity. In contrast, activation of Mn2+-stimulated adenylate cyclase by 30 mM (NH4)2SO4 also reduced sensitivity to inhibition by 2',5'-ddAdo(IC50 1.1 microM).(ABSTRACT TRUNCATED AT 400 WORDS)

Acrosin↗
PubMed1989

An asymmetric synthesis of (R) and (S)-1-alkoxy-2,3-propanediols including precursors to platelet activating factor.

The titanium-assisted nucleophilic opening of glycidol with primary aliphatic alcohols gives 1-alkoxy-2,3-propanediols. The titanium alkoxide used in the reaction should be the alkoxide of the alcohol used for the reaction. When optically active (S)-glycidol is used in the reaction, (S)-1-alkoxy-2,3-propanediols are obtained without loss of optical activity. When the reaction is carried out at 70-75 degrees C without solvent, the 1-alkoxy-2,3-propanediols are obtained in yields of 45-59%. The regioisomeric 2-alkoxy-1,3-propanediols are found to the extent of 4-6% in the reaction. The optical purity of glycidol can be measured from the high field (500 MHz) nuclear magnetic resonance spectrum of the Mosher ester.

Chemical Phenomena↗
PubMed1989

Hematologic manifestations of malignancy.

Hematologic dysfunction occurs commonly in patients with malignancy. Over half are anemic, often because of acute or chronic blood loss, marrow involvement by the malignancy, marrow suppressive effects of chemotherapy or radiation therapy, or because of the anemia of chronic disease. Less frequently, anemia may result from red cell aplasia, folate or B12 deficiency, hemolytic processes, or hypersplenism. Occasional patients may become polycythemic because of erythropoietin-producing tumors such as renal adenocarcinomas or cerebellar hemangiomas. Elevation of the white cell count is commonly seen, especially in patients with lung cancer. Monocytosis and thrombocytosis, which may be early signs of an underlying malignancy, are also very common and occur in up to half of patients. Thrombocytopenia is commonly a result of therapy or marrow replacement; a few patients may have a syndrome resembling immune thrombocytopenic purpura. Abnormalities of coagulation are present in many patients, and may lead to superficial or deep venous thromboses, pulmonary emboli, nonbacterial thrombotic endocarditis with arterial emboli, bleeding, or acute disseminated intravascular coagulation. A sound understanding of the potential hematologic complications that can result from the malignant process is essential to the clinician caring for cancer patients.

Anemia↗
PubMed1989

Epidemiology and diagnosis of acute conjunctivitis at an inner-city hospital.

Chlamydia has been found to be the cause of a high percentage of cases of neonatal and chronic conjunctivitis in an inner-city population. To assess the etiology and epidemiology of acute conjunctivitis in this population, conjunctival scrapings were sampled from 45 patients presenting to an ocular emergency room; and replicate chlamydial, viral, and bacterial cultures and cytology tests were done. No cases of chlamydial conjunctivitis were diagnosed, although a viral etiology was established in 36% of the cases and a bacterial etiology in 40%. Twenty-four percent of the cases were not diagnosed. The authors recommend limiting the initial laboratory workup of patients with acute conjunctivitis to obtaining conjunctival smears for Gram and Giemsa staining. Chlamydial direct immunofluorescent monoclonal antibody (DFA) should be done if the patient is sexually active. Hyperacute conjunctivitis or acute conjunctivitis refractory to treatment mandates a more complete set of laboratory tests.

Acute Disease↗
PubMed1989

Antagonism of moderate degrees of vecuronium-induced neuromuscular block by small doses of neostigmine.

We have studied the influence of a reduced dose of neostigmine on recovery from vecuronium-induced neuromuscular block in 26 adult patients, using electromyographic responses to train-of-four (TOF) stimulation. Neostigmine 10, 20 or 40 micrograms kg-1 was administered when the first response had recovered spontaneously to 5-10% or 40-50% of control. Antagonism was accepted as adequate when the first response reached 90% of control and the TOF ratio reached 0.7. At both degrees of spontaneous recovery, neostigmine 40 micrograms kg-1 evoked the most rapid antagonism. Clinical recovery was satisfactory with no differences between groups. Block produced by neostigmine was not observed. The pattern of recovery of the single response and the TOF ratio was not altered by neostigmine in the range of doses studied. We suggest that the dose of neostigmine should not be reduced below 40 micrograms kg-1 even when all responses of the TOF are present.

Adult↗
PubMed1989

Tumors producing human tumor necrosis factor induced hypercalcemia and osteoclastic bone resorption in nude mice.

We used a Chinese hamster ovary cell line that had been transfected with the human tumor necrosis factor (TNF) gene and constitutively produced TNF when transplanted in nude mice to study the effects of continuous production of TNF on calcium homeostasis. Continuous exposure to TNF caused increased osteoclastic bone resorption and humoral hypercalcemia in these animals. The mice bearing TNF-producing tumors were significantly hypercalcuric compared to mice bearing control tumors, but urinary cAMP excretion was unchanged. Mice bearing Chinese hamster ovary cell tumors containing the empty vector did not demonstrate hypercalcemia or increased bone resorption. This model system using transfected cells to continuously produce cytokines in vivo is more analogous to the pathophysiological conditions present in patients than intermittent injections and can produce much longer exposures than infusion pumps. Such model systems should allow a better understanding of the role of factors involved in humoral hypercalcemia.

Animals↗