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Biomedical subjects

J D Johnson

Publications and source records attributed to J D Johnson.

At least 253 records · Page 14Linked to original sources
PubMed1984

Fungal splenic abscess.

Nineteen patients with fungal splenic abscesses included 16 with leukemia, one drug user, one patient with Cushing's syndrome, and one without predisposing causes. Fifteen had persistent fever; six had esophageal or mucocutaneous candidiasis. Abdominal pain occurred in seven patients, splenomegaly occurred in six, and left abdominal mass occurred in one. Three chest x-ray films showed left pleural effusions; two had elevated left hemidiaphragms, two had left-sided infiltrates, and one was normal. Sixteen of 17 technetium Tc 99m sulfur colloid scans were abnormal, as were 15 gallium citrate Ga 67 scans. Two computed tomographic studies revealed splenic defects. Candida was the cause in 15 cases, Aspergillus was the cause in three cases, and Blastomyces dermatitidis was the cause in one case. Sixteen patients underwent splenectomy, 12 receiving postoperative antifungal therapy. Fifteen survived regardless of underlying disease or hepatic microabscesses.

Abscess↗
PubMed1983

The role of non-coding DNA sequences in transcription and processing of a yeast tRNA.

We have tested the hypothesis that conserved sequences in the intervening sequence (IVS) and 5'-flanking region of a yeast tRNALeu3 gene serve some function. Genes with deletions of 8, 10, 13 and 20 bp in the IVS are all active as templates in vitro. Yeast extracts produce mature tRNALeu3 from delta 8, delta 10 and delta 13 genes. Xenopus extracts do not detectably ligate the 5' and 3' half-molecules resulting from IVS excision. Neither extract is able to excise the IVS from delta 20 precursors. Genes with introns enlarged by 10, 21 or 30 bp of DNA produce mature tRNA. Insertion of 103 bp results in reduced levels of transcription, little if any end maturation, and no detectable mature product. A conserved 15 bp sequence is present at the 5'-end of the tRNA sequence. Replacement of yeast DNA up to position -22 leaves the tRNA gene transcriptionally active. With replacement extended to -2 the gene is active in Xenopus extracts but nearly inert in yeast extracts. We conclude that tRNA transcription in yeast is insensitive to IVS structure but can be positively influenced by 5'-flanking sequence.

Animals↗
PubMed1983

Local application of cyclic AMP in the rat brain: characterization of the cardiovascular response.

Previous studies have demonstrated that central administration of dibutyryl cyclic AMP (DBcAMP) produces a dose-dependent rise in blood pressure accompanied by tachycardia. In an attempt to delineate brain sites that mediate these cardiovascular responses, DBcAMP was stereotaxically injected into local brain areas. Injections of 100 micrograms into the right lateral, third, and fourth ventricles produced pressor responses. Perfusion of the brain from the lateral ventricle to the cisterna magna with 15 micrograms/25 microliters per min induced a rise in blood pressure and significant bradycardia. The cyclic nucleotide was injected unilaterally in doses of 10, 25, and 50 micrograms into the posterior hypothalamic nucleus (PHN), anterior hypothalamic area (AHA), locus coeruleus (LC), and nucleus tractus solitarii (NTS). PHN injections induced tachycardia with minimal changes in blood pressure. Bradycardia and a depressor response were observed following injection of the 10 micrograms dose into the LC. Within the AHA, DBcAMP (10 micrograms) did not induce significant changes in cardiovascular function. Additionally, injections into the NTS initiated a biphasic depressor-pressor effect. Within these sites, cardiovascular responses to the 10 micrograms dose of DBcAMP paralleled those observed after adrenergic activation. These results strongly suggest that cyclic AMP functions as a second messenger within select central cardiovascular regulatory sites and plays an important role in cardiovascular regulation.

Animals↗
PubMed1983

A fluorescent calmodulin that reports the binding of hydrophobic inhibitory ligands.

Ca2+ binding to calmodulin in the pCa range 5.5-7.0 exposes hydrophobic sites that bind hydrophobic inhibitory ligands, including calmodulin antagonists, some Ca2+-antagonists and calmodulin-binding proteins. The binding of these hydrophobic ligands to calmodulin can be followed by the approx. 80% fluorescence increase they produce in dansylated (5-dimethylaminonaphthalene-1-sulphonylated) calmodulin (CDRDANS). In the presence of Ca2+, calmodulin binds the calmodulin inhibitor, R24571, with an affinity of approx. 2-3 nM and hydrophobic ligands, including trifluoperazine (TFP), W-7 [N-(6-aminohexyl)-5-chloronaphthalene-1-sulphonamide], fendiline, felodipine and prenylamine, with affinities in the micromolar range. This binding is strongly Ca2+-dependent and Mg2+-independent. Calmodulin shows a reasonably high degree of specificity in its binding of these ligands over other ligands tested. CDRDANS, therefore, provides a convenient and simple means of monitoring the interaction of a variety of hydrophobic ligands with the Ca2+-dependent regulatory protein, calmodulin. CDRDANS binds to phospholipid vesicles made of (dimyristoyl)phosphatidylcholine (DMPC) or (dipalmitoyl)phosphatidylcholine (DPPC) and produces fluorescence increases only in the presence of Ca2+ and at temperatures above their gel-to-liquid crystalline phase transition. Although the fluorescence changes in CDRDANS accurately report phase transitions in these liposomes, its binding to these vesicles is weak. Calmodulin probably requires a high-affinity lipid-bound receptor protein for its high-affinity binding to natural membranes.

Anilino Naphthalenesulfonates↗
PubMed1983

Allosteric interactions among drug binding sites on calmodulin.

Felodipine is a fluorescent dihydropyridine Ca2+-antagonist. It binds to calmodulin in a Ca2+-dependent manner, and undergoes a fluorescence increase which allows us to monitor its interaction with calmodulin. Hydrophobic ligands including the calmodulin antagonist, R24571 and Ca2+ antagonists, prenylamine and diltiazem, bind to calmodulin and potentiate felodipine binding by as much as 20 fold. These studies suggest that allosteric interactions occur among different drug binding sites on calmodulin. Our results are discussed in terms of the mechanism of action of calmodulin.

Allosteric Site↗
PubMed1983

Effect of patent ductus arteriosus on left ventricular output in premature infants.

A 5 MHz range-gated portable pulsed Doppler velocity meter was used to measure mean ascending aortic blood flow velocity noninvasively. Studies were performed from a suprasternal approach in 18 preterm infants with patent ductus arteriosus. Measurements were made in each patient before and after medical or surgical closure of the PDA. The internal ascending aortic diameter was determined echocardiographically and aortic cross-sectional area calculated according to the equation AAo = pi d2/4. Ascending aortic blood flow was computed as QAo (ml/min) = VAo (cm/sec) x AAo (cm2) x 60 (sec/min). Prior to PDA closure, QAo averaged 343 ml/min/kg, well above predicted normal values. After PDA closure, QAo fell to 252 ml/min/kg, significantly lower than the preclosure level (P less than 0.001), but slightly higher than the mean cardiac output of healthy newborn infants. The mean QAo after surgical ligation of the PDA was closer to the predicted normal value than after treatment with indomethacin alone. This study reflects the effect of left-to-right ductus shunting on left ventricular output and emphasizes the demands placed on the neonatal left ventricle by PDA.

Cardiac Output↗
PubMed1983

Metabolic acidosis in the newborn period.

In this chapter we have described the metabolic diseases which are known to have caused acidosis during the newborn period. We have also provided some diagnostic and treatment guidelines. The occurrence of acidosis in a newborn baby should initiate several actions, aimed simultaneously at treatment and diagnosis. An initial blood gas determination, accompanied by the results of serum electrolytes and glucose, will, in most instances, separate respiratory from metabolic causes. Finding of an increased anion gap and/or presence of hypoglycaemia should direct attention towards errors in intermediary metabolism.

Acidosis↗
PubMed1983

Developmental changes in bilirubin production in the rat.

Total bilirubin production and relative rates of early labeling of bilirubin (ELB) were determined in rats during postnatal development. Total production was estimated by measuring endogenous rate of excretion of carbon monoxide (VeCO), while ELB was determined by measuring the incorporation of glycine-2-14C and delta-aminolevulinic acid-5-14C(delta-ALA-5-14C) into expired 14CO over a 30-h period after isotope injection. VeCO was considerably higher in 1- and 4-day-old rat pups than in adults, but fell rapidly toward adult values by 9 days of age. 14CO excretion from both isotopic precursors of bilirubin was significantly greater in suckling animals than in postweanling and young adult animals when expressed as a percent of the administered radioactivity. The activity of hepatic heme oxygenase showed a similar pattern of postnatal change to 14CO excretion from both glycine-2-14C and delta-ALA-5-14C. However, phenobarbital administration to young weanling animals significantly increased 14CO excretion from glycine-2-14C, but did not result in a change in the activity of hepatic heme oxygenase. The activity of hepatic heme oxygenase does not always reflect in vivo ELB.

Age Factors↗
PubMed1983

Bioassay and dose measurement in UV disinfection.

A bioassay method was developed to measure the average intensity within a UV disinfection reactor. The survival of spores of Bacillus subtilis was determined as a function of UV dose to prepare a standard curve. Spores were added to unknown systems, and the survival rate was used to determine the average intensity. A modification was used for flow-through reactors by which spores were injected as a spike and collected at a known time after injection. A point source summation method for calculating intensity was verified by bioassay measurements in a simple cylinder. This calculation method was also applied to multiple-lamp reactors.

Bacillus subtilis↗
PubMed1983

Calmodulin, Ca2+-antagonists and Ca2+-transporters in nerve and muscle.

Calcium is of fundamental importance in the regulation of both muscle contraction and neurosecretion. Its control of these processes is achieved by its binding and activation of various Ca2+-binding proteins (CBP), including those in the Ca2+ channel, the Na+-Ca2+ antiporter, and intracellular calmodulin (CDR). Generally, Ca2+-binding to regulatory CBP exposes hydrophobic sites on their surface at which the CBP interfaces with its receptor or binds inhibitory hydrophobic ligands. We find that some Ca2+-antagonist drugs (Ca-ANT) bind to and inhibit calmodulin and that some calmodulin antagonists (CDR-ANT) block Ca2+ channels. This suggests that CDR and the CBP that regulate the Ca2+ channel may be quite homologous proteins, Ca-ANT and CDR-ANT are not effective inhibitors of the Na+-Ca2+ antiporters of heart sarcolemma and brain synaptosomes, suggesting that these antiporters are fundamentally different from the antiporter of heart mitochondria. These results are discussed in terms of Ca2+-binding proteins being potential targets for pharmacological interventions designed to block specific aspects of the action of calcium.

Action Potentials↗
PubMed1983

Breath hydrogen analysis: a review of the methodologies and clinical applications.

Hydrogen gas (H2) is a product of the fermentation of dietary carbohydrate (CHO) by bacteria in the lumen of the gastrointestinal tract in man. Thus, H2 is actually an exogenously produced gas, which either is passed as flatus, or diffuses into the body and is exhaled. In the adult, a fairly constant fraction is expired, providing a reliable indicator of total colonic H2 production. Breath H2 analysis currently represents a useful clinical means of testing adults and older children for the malabsorption of CHO. Noninvasive and easy procedures for the collection of expired air have encouraged their increasingly widespread use in pediatrics. Evidence to date suggests that breath H2 analysis may provide the best available method for estimating semiquantitatively the degree of CHO malabsorption. The association of the results of breath H2 analysis with other clinical measures of CHO digestion and absorption is expected, but discrepancies can also be anticipated based on the nature of this particular trace gas method. The interpretation of the results of breath H2 analysis in neonates and young infants remains especially problematic because of confounding variables which are difficult to control and are measured infrequently.

Adult↗
PubMed1983

Splenic abscess complicating infectious endocarditis.

Infective endocarditis is the most common condition predisposing a patient to splenic abscess, and the conditions of 37 such patients are reviewed herein. Streptococci accounted for 18 abscesses, with six containing enterococci; 12 other contained staphylococci. Symptoms suggesting splenic abscess include abdominal distention, hiccups, and pain in the left flank, abdomen, and shoulder. Physical signs include recurrent or persistent fever and abdominal tenderness, with splenomegaly often inapparent. The most frequent finding on x-ray film is pleural effusion on the left side. Seventeen patients not undergoing splenectomy died; in these, the diagnosis of splenic abscess was established postmortem. Twenty patients underwent splenectomy, 19 of whom received antibiotics and survived; one patient who was not treated with antibiotics died. Physicians should suspect splenic abscess in patients with endocarditis, particularly those with staphylococcal or enterococcal endocarditis. Those patients with clinical evidence suggestive of splenic abscess should undergo specific diagnostic studies, and exploratory laparotomy may be necessary.

Abscess↗
PubMed1983

Calcium and calmodulin antagonists binding to calmodulin and relaxation of coronary segments.

Ca++ antagonist drugs (also known as Ca++ channel blockers) and the calmodulin antagonists trifluoperazine (TFP) and W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide] were capable of half-maximally relaxing porcine coronary segments at 1.5 X 10(-10) M for felodipine, 6.5 X 10(-8) M for verapamil, 2.6 X 10(-7) M for diltiazem, 7 X 10(-7) M for prenylamine, 7 X 10(-6) M for TFP and 45 X 10(-6) M for W-7. Their correspondent binding to calmodulin was half-maximal at 2.8 X 10(-6), 30 X 10(-6), 80 X 10(-6), 5 X 10(-7), 5.0 X 10(-6) and 11 X 10(-6) M, respectively. Only prenylamine, TFP and W-7 were capable of relaxing coronaries over the same concentration range in which they bind to calmodulin. The relaxations produced by these calmodulin antagonists and prenylamine could not be overcome by contractile agonists which release Ca++ from internal stores (histamine and serotonin), whereas the relaxations produced by felodipine, verapamil and diltiazem were readily reversed by either of these agonists. This is consistent with TFP and W-7 and to some degree prenylamine-inducing vasodilation by calmodulin antagonism and with felodipine, verapamil and diltiazem vasodilating through Ca++ antagonism of Ca++ channels at the level of the cell membrane.

Animals↗
PubMed1982

Immunological studies on bovine milk lipoprotein lipase. Effects of Fab fragments on enzyme activity.

Rabbit antiserum was prepared against purified bovine mild lipoprotein lipase. Immunoelectrophoresis of lipoprotein lipase gave a single precipitin line against the antibody which was coincident with enzyme activity. The gamma-globulin fraction inhibited heparin-releasable lipoprotein lipase activity of bovine arterial intima, heart muscle and adipose tissue. The antibody also inhibited the lipoprotein lipase activity from adipose tissue of human and pig, but not that of rat and dog. Fab fragments were prepared by papain digestion of the gamma-globulin fraction. Fab fragments inhibited the lipoprotein lipase-catalyzed hydrolysis of dimyristoylphosphatidylcholine vesicles and trioleoylglycerol emulsions to the same extent. The Fab fragments also inhibited the lipolysis of human plasma very low density lipoproteins. The change of the kinetic parameters for the lipoprotein lipase-catalyzed hydrolysis of trioleoylglycerol by the Fab fragments was accompanied with a 3-fold increase in Km and a 10-fold decrease in Vmax. Preincubation of lipoprotein lipase with apolipoprotein C-II, the activator protein for lipoprotein lipase, did not prevent inhibition of enzyme activity by the Fab fragments. However, preincubation with dipalmitoylphosphatidylcholine-emulsified trioleoylglycerol or Triton X-100-emulsified trioleoylglycerol had a protective effect (remaining activity 7.0 or 25.8%, respectively, compared to 1.0 or 0.4% with no preincubation). The addition of both apolipoprotein C-II and substrate prior to the incubation with the Fab fragments was associated with an increased protective effect against inhibition of enzyme activity; remaining activity with dipalmitoylphosphatidylcholine-emulsified trioleoylglycerol was 40.6% and with Triton X-100-emulsified trioleoylglycerol, 45.4%. Human plasma very low density lipoproteins also protected against the inhibition of enzyme activity by the Fab fragments. These immunological studies suggest that the interaction of lipoprotein lipase with apolipoprotein C-II in the presence of lipids is associated with a conformational change in the structure of the enzyme such that the Fab fragments are less inhibitory. The consequence of a conformational change in lipoprotein lipase may be to facilitate the formation of an enzyme-triacylglycerol complex so as to enhance the rate of the lipoprotein lipase-catalyzed turnover of substrate to products.

Animals↗
PubMed1982

Selective inhibition of Na+-induced Ca2+ release from heart mitochondria by diltiazem and certain other Ca2+ antagonist drugs.

The effect of Ca2+ antagonist drugs on Ca2+ uptake and Na+-induced Ca2+ release by isolated rabbit heart mitochondria has been studied using arsenazo III and dansylaziridine-labeled troponin C as Ca2+ indicators. Mitochondria accumulated 20 nmol of Ca2+/mg of protein by a respiration-dependent process. A23187, carbonyl cyanide p-trifluoromethoxyphenylhydrazone, or Na+ induced a release of Ca2+ from Ca2+-loaded and ruthenium red (RR)-treated mitochondria. Ca2+ antagonist drugs had no effect on the Ca2+ uptake process or on Ca2+ release induced either by A23187 or by carbonyl cyanide p-trifluoromethoxyphenylhydrazone but they were effective in inhibiting the Na+-induced Ca2+ release process. The drug concentrations that resulted in 50% inhibition of Na+-induced Ca2+ release were 7, 12, 13, 66, and 150 microM for diltiazem, prenylamine, fendiline, nifedipine, and verapamil, respectively. In the absence of RR, the net amount of Ca2+ released by Na+ was less than that which occurred in the presence of RR due to the simultaneous operation of both the Ca2+ uptake and the Ca2+ release processes. Under these conditions, the inhibition of Ca2+ uptake by RR brought about a complete release of Ca2+ from the mitochondria, and the inhibition of the Na+-induced Ca2+ release by diltiazem resulted in an apparent uptake of Ca2+ by the mitochondria. These results indicate that diltiazem and certain other Ca2+ antagonist drugs may be selective inhibitors of the Na+/Ca2+ antiporter in heart mitochondria much like ruthenium red is a selective inhibitor of the Ca2+ uniporter.

Animals↗