Mediator release in aspirin-induced reactions.
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Anaphylaxis↗
Biomedical subjects
C M Smith
Publications and source records attributed to C M Smith.
DNA damage-inducible loci in Salmonella typhimurium.
lac operon fusions to DNA damage-inducible (din) loci were generated in Salmonella typhimurium LT2. Many of these din fusions were efficiently repressed by cloned Escherichia coli LexA, while others were not; all required RecA for induction. Several din fusions exhibited strong inducibility and will be useful in developing an SOS induction assay in S. typhimurium to detect genotoxins.
Alkylating Agents↗
Seroreactive recombinant herpes simplex virus type 2-specific glycoprotein G.
The herpes simplex virus type 2 (HSV-2) genome codes for an envelope protein, glycoprotein G (gG), which contains predominantly type 2-specific epitopes. A portion of this gG gene has been expressed as a fusion protein in Escherichia coli. Expression was regulated by a lambda phage pL promoter. The 60,000-molecular-weight recombinant protein was purified by ion-exchange chromatography. Amino acid sequence analysis confirmed the N terminus of the purified protein. Mice immunized with recombinant gG developed antibodies reactive with native HSV-2 protein, but not with HSV-1 protein, in an indirect immunofluorescence assay. The serological activity of this purified recombinant gG protein was evaluated by immunoblot assay. This protein was reactive with an HSV-2 gG monoclonal antibody. It was also reactive with HSV-2 rabbit antiserum but not with HSV-1 rabbit antiserum. Of 15 patient serum samples known to have antibody to HSV-2, 14 were reactive with this recombinant type 2-specific gG protein, and none of 15 HSV antibody-negative patient serum samples showed reactivity. In agreement with the expected prevalence of HSV-2 infection, 27.6% of 134 serum samples from random normal individuals had antibodies reactive with recombinant gG. This recombinant gG protein may be of value in detecting HSV-2-specific antibody responses in patients infected with HSV-2.
Adult↗
A dose ranging study of ibuprofen suspension as an antipyretic.
A double blind trial was conducted to determine the dose of ibuprofen suspension, which is effective in reducing the body temperature. The principal measure of efficacy was a reduction in axillary temperature of 1 degree C or more three hours after dosing. A second objective of the trial was to compare the incidence and severity of side effects and the palatability of a range of ibuprofen doses. Ninety three children were included in the analysis. All four doses of ibuprofen studied (0.625 mg/kg-5 mg/kg) were associated with temperature reduction and only the lowest dose failed to satisfy the principal measure of efficacy. The influence of dose on the magnitude of the body temperature reduction was significant and the 5 mg/kg dose achieved the largest mean reduction in body temperature (2 degrees C). The tolerability and palatability of all doses studied were excellent. These findings suggest that ibuprofen is a good alternative to paracetamol as an antipyretic.
Child, Preschool↗
Osmotic challenges in the assessment of bronchial hyperresponsiveness.
It is now well recognized that a change in osmolarity of the periciliary fluid is a potent stimulus to airway narrowing and may be a common cause for provoking an attack of asthma. This has led to the use of nonisotonic aerosols to document bronchial hyperresponsiveness in patients with clinical asthma. These aerosols are generated by ultrasonic nebulizers, and the most commonly used are water, hyperosmolar sodium or potassium chloride, and dextrose. An increase in specific airway resistance of 100% or a reduction in FEV1 of 20% is considered as an abnormal response to these aerosols. There are a number of factors that affect the airway response to these aerosols, and these include the osmolarity of the solution and its ionic content and pH. In addition responses may be affected by a previous challenge or medication. It is not known precisely how these aerosols act to induce airway narrowing, but it is not by a direct action on smooth muscle. It is thought that a change in osmolarity of the airways causes the release of inflammatory mediators, which then act to narrow the airways. For this reason challenge by nonisotonic aerosols is different from challenge by histamine and methacholine and may be preferable for the diagnosis of asthma and assessment of its treatment.
Adrenergic beta-Agonists↗
Characteristics of bronchial hyperresponsiveness in chronic obstructive pulmonary disease and in asthma.
By studying the characteristics of BHR in subjects clearly defined as having asthma or COPD, it is apparent that there are both similarities and differences. These responses can be broadly explained in terms of present knowledge of the pathologic features and the mechanisms causing the abnormalities in the two diseases, and they highlight the important differences between the diseases. It seems likely that tests of BHR with histamine and methacholine cannot be used to distinguish asthma from COPD in subjects with a mild decrease in FEV1 and symptoms that do not clearly suggest asthma or COPD. However, a dose-response curve to methacholine is helpful. If there is a plateau, and the PD20 FEV1 is more than 4.0 mumol, it is unlikely to be asthma. If there is no plateau, a test with propranolol or SO2 may be useful to discriminate the two diseases. The similarities in the responses-especially those to histamine-explain why there is frequently difficulty in deciding the nature of the disease present in an individual subject. Is it important to distinguish the two diseases? In the introduction it was suggested that it is important for understanding these diseases, for prognosis, for treatment, and ultimately for prevention. It remains difficult to determine prognosis from any single test of bronchial responsiveness, and response to prophylaxis (stopping smoking, allergen avoidance) plus drug treatment over several years is probably needed to predict outcome in an individual patient. Finally, despite the valid hypothesis proposed by Orie and coworkers (2), it seems unlikely that studying the characteristics of BHR will shed light on the "host" factors present in both diseases that remain poorly understood.
Asthma↗
The potent and selective sulfidopeptide leukotriene antagonist, SK&F 104353, inhibits aspirin-induced asthma.
We have determined the effect of prior inhalation of the LTD4 antagonist SK&F 104353 on the response to aspirin ingestion in six aspirin-sensitive asthmatic subjects (five women and one man 31 to 54 yr of age) in a randomized, double-blind, cross-over, placebo-controlled study. Pretreatment with inhaled SK&F 104353 (average nebulized dose, 893 micrograms) inhibited the response by a mean of 47% (p = 0.02). The inhibition was partial, ranging from 43 to 74% in five subjects. In the remaining subject, there was no effect of the drug on the asthmatic response. We conclude that the mechanism of aspirin-induced asthma is at least partially mediated by the leukotrienes in the majority of susceptible patients and that leukotriene antagonists may be useful in the treatment of aspirin-induced asthma.
Adult↗
Urinary leukotriene E4 levels after allergen and exercise challenge in bronchial asthma.
Urinary leukotriene E4 (LTE4) concentrations were measured in six asthmatic subjects after treadmill exercise, and in five asthmatic subjects after allergen challenge. Exercise and allergen challenge produced a 42 +/- 18% (mean +/- SD) and 22 +/- 8% fall in FEV1, respectively. The baseline concentration of urinary LTE4 in subjects challenged with exercise was 64 (27 to 150) pg/mg creatinine (geometric mean and 95% confidence interval), and in those challenged with allergen it was 36 (23 to 59) pg/mg creatinine. Urinary LTE4 concentrations did not change significantly in the 24 h after exercise. In contrast, there was a mean 4-fold increase in urinary LTE4 during the 3 h after allergen challenge.
Adult↗
Gliomatosis cerebri: a clinical, radiological and pathological report of four cases.
Four cases of gliomatosis cerebri are described. In only one case was the diagnosis made during life. Radiological investigations, including computed tomography and magnetic resonance imaging, showed non-specific changes in the white matter.
Adolescent↗
Determination of the catalytic pathway of C4-leaf pyruvate, orthophosphate dikinase from maize.
The mechanism of the maize pyruvate, phosphate dikinase-catalyzed conversion of adenosine 5'-triphosphate, orthophosphate and pyruvate to adenosine 5'-monophosphate, inorganic pyrophosphate and phosphoenolpyruvate, respectively, was determined by using transient kinetic techniques. The data obtained demonstrate that catalysis in the maize pyruvate, phosphate dikinase active site involves initial transfer of the P beta P-unit from adenosine 5'-trisphosphate to the enzyme to form a pyrophosphorylenzyme intermediate, followed by sequential phosphoryl group transfer to orthophosphate (to form pyrophosphate and a phosphoenzyme intermediate) and pyruvate (to form phosphoenolpyruvate and free enzyme).
Kinetics↗
Mast cells and pulmonary fibrosis. Identification of a histamine releasing factor in bronchoalveolar lavage fluid.
As elevated bronchoalveolar lavage (BAL) fluid histamine levels are noted in patients with pulmonary fibrosis (PF), we assayed BAL fluid from 16 patients with PF for the presence of a histamine releasing factor (HRF). HRF activity was assayed by measuring release of the preformed mast cell-derived mediators, histamine, or beta-hexosaminidase (beta-hex) from a purified population of IL-3 dependent mouse bone marrow derived mast cells (MBMMC) or human blood basophils. Mean BAL cell free histamine levels in the patients with PF was 1226 +/- 1349 pg/ml, whereas BAL histamine levels in a comparison group of six non-PF patients was 118 +/- 60 pg/ml. HRF was significantly elevated in BAL fluid of patients with PF (mean beta-hex release 24.5 +/- 12.9%; range 6.8 to 52.4%) compared to the non-PF group of patients (mean beta-hex release 7.9 +/- 7.7%; range 1.8 to 20.7%). The PF HRF not only degranulated MBMMC, but also induced the generation of the arachidonic acid metabolite leukotriene C4 from MBMMC (24.6 +/- 4.2 ng leukotriene C4/10(6) MBMMC). The PF HRF did not appear to be a cytokine previously identified in BAL fluid of patients with PF (i.e., platelet derived growth factor or insulin growth factor-1) or a human cytokine able to degranulate human basophils (i.e., IL-1, or granulocyte-macrophage-CSF) as these recombinant human cytokines did not induce MBMMC beta-hex release. Physicochemical characterization of the HRF revealed that it was relatively heat stable, pronase sensitive and on Sephadex G-75 and G-200 column chromatography had an apparent molecular mass of 30 to 50 kDa. The ability of PF BAL to induce beta-hex release from MBMMC was not dependent on IgE as unsensitized or lactic acid treated MBMMC release similar amounts of beta-hex compared to MBMMC sensitized with IgE. Thus, BAL fluid of patients with PF contains an HRF that induces beta-hex release from MBMMC via an IgE-independent mechanism. The presence of the HRF could explain elevated BAL histamine levels in patients with PF.
Bronchoalveolar Lavage Fluid↗
Fibrinolysis by tissue plasminogen activator in a child with pulmonary embolism.
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Catheterization, Swan-Ganz↗
Abnormality of von Willebrand factor in patients with hemoglobin E-beta (0) thalassemia.
The authors have identified six Southeast Asian patients ranging in age from 14 to 21 years with hemoglobin E-beta(0) thalassemia and a coagulopathy involving von Willebrand factor (vWF). These patients had normal or only slightly decreased plasma clotting factor levels. The activated partial thromboplastin time was prolonged in four of the patients. The abnormal feature common to all patients was a qualitative loss of high molecular weight multimers of vWF by crossed immunoelectrophoresis (vWF:CIE). Plasma vWF antigen concentration (vWF:Ag) and ristocetin cofactor activity (vWF:RCo) also were decreased and bleeding time prolonged in three patients. Epistaxis was present in two. No family history of increased bleeding tendency was present in any patient. Coagulation parameters and vWF:CIE were normal in two first-degree relatives without this hemoglobinopathy. vWF abnormalities and clinical manifestations were greatest in those patients with the most severe anemia and hepatosplenomegaly. These six patients appear to have an acquired abnormality of vWF, although they lack the clinical characteristics of acquired von Willebrand disease. While the etiology of this abnormality is unclear, the authors speculate that proteolysis of vWF secondary to extramedullary hematopoiesis or loss through high cardiac output shear stress in these anemic patients may be involved.
Adolescent↗
Pantothenate kinase activity in livers of genetically diabetic mice (db/db) and hormonally treated cultured rat hepatocytes.
Preparations from livers of fed and fasted genetically diabetic and nondiabetic mice (C57BL/KsJ db/db, db/+, or +/+) were used to determine whether changes in pantothenate kinase activity and/or properties corresponded to hormonally directed changes in liver total CoA content. Livers of fasted, nondiabetic mice had ratios of pantothenate kinase (PAK) to lactate dehydrogenase (LDH) activity 1.6 times values for fed nondiabetic controls, and they had a total CoA content per milligram of DNA that was 1.8 times control values. Livers of fed genetically diabetic mice had values for PAK/LDH and total CoA per milligram of DNA that were 1.5 and 2.8 times, respectively, those of nondiabetic controls. Liver PAK from genetically diabetic mice was inhibited by acetyl-CoA to the same extent as enzyme from nondiabetic mice and by CoASH to nearly the same extent. Rat hepatocytes in primary culture incubated with dibutyryl cAMP + theophylline + dexamethasone had PAK/LDH levels 1.5 times those of cells not treated with hormonal effectors, and PAK was inhibited to the same extent by acetyl-CoA and nearly the same extent by CoASH. The data show an increase in extractable hepatic PAK activity under conditions in which the total CoA content is elevated, and they suggest that glucocorticoids and cAMP levels contribute to the increased PAK activity.
Acetyl Coenzyme A↗
A useful technique for improving the diagnostic yield from single stereotactic biopsies of brain.
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Biopsy↗
Utility of the Self-Administered Alcoholism Screening Test (SAAST) in schizophrenic patients.
The utility of the Self-Administered Alcoholism Screening Test (SAAST) in determining alcohol abuse and alcoholism was assessed in a preliminary study of 21 schizophrenic patients during their hospitalization in an acute care psychiatric unit; on admission all met DSM-III-R criteria for schizophrenia and none were detected to have any alcohol-related diagnosis. SAAST scores ranged from 2 to 26 with a mean score of 10.8. Forty-eight percent (10/21) had SAAST scores greater than or equal to 10, indicating "probable alcoholism"; 62% (13/21) scored 8 or higher. Every patient with a SAAST score of 8 or higher also met DSM-III-R criteria for alcohol abuse or dependence on the basis of patient interview, independent chart reviews, and interviews of significant others. In contrast, only half (5/10) of the high SAAST scorers would actually admit to a problem with drinking during the extensive study interviews. Six SAAST items were found to be highly predictive of abuse or alcoholism; the SAAST had greater sensitivity than the interviews. Sixty-two percent (8 of 13) of the schizophrenic patients who met the DSM-III-R criteria for alcohol abuse reported a first degree relative with an alcohol-related problem, in contrast to only 25% of the "nonalcoholic" patients. The patterns of the alcoholic schizophrenic patients' responses on the different SAAST items revealed even greater denial and lack of insight than those of nonschizophrenic alcoholic subjects.
Adult↗
Sequence analysis and mapping of the Salmonella typhimurium LT2 umuDC operon.
In Escherichia coli, efficient mutagenesis by UV requires the umuDC operon. A deficiency in umuDC activity is believed to be responsible for the relatively weak UV mutability of Salmonella typhimurium LT2 compared with that of E. coli. To begin evaluating this hypothesis and the evolutionary relationships among umuDC-related sequences, we cloned and sequenced the S. typhimurium umuDC operon. S. typhimurium umuDC restored mutability to umuD and umuC mutants of E. coli. DNA sequence analysis of 2,497 base pairs (bp) identified two nonoverlapping open reading frames spanning 1,691 bp that were were 67 and 72% identical at the nucleotide sequence level to the umuD and umuC sequences, respectively, from E. coli. The sequences encoded proteins whose deduced primary structures were 73 and 84% identical to the E. coli umuD and umuC gene products, respectively. The two bacterial umuDC sequences were more similar to each other than to mucAB, a plasmid-borne umuDC homolog. The umuD product retained the Cys-24--Gly-25, Ser-60, and Lys-97 amino acid residues believed to be critical for RecA-mediated proteolytic activation of UmuD. The presence of a LexA box 17 bp upstream from the UmuD initiation codon suggests that this operon is a member of an SOS regulon. Mu d-P22 inserts were used to locate the S. typhimurium umuDC operon to a region between 35.9 and 40 min on the S. typhimurium chromosome. In E. coli, umuDC is located at 26 min. The umuDC locus in S. typhimurium thus appears to be near one end of a chromosomal inversion that distinguishes gene order in the 25- to 35-min regions of the E. coli and S. typhimurium chromosomes. It is likely, therefore, that the umuDC operon was present in a common ancestor before S. typhimurium and E. coli diverged approximately 150 million years ago. These results provide new information for investigating the structure, function, and evolutionary origins of umuDC and for exploring the genetic basis for the mutability differences between S. typhimurium and E. coli.
Amino Acid Sequence↗
Serological evaluation of Escherichia coli-expressed human T-cell leukemia virus type I env, gag p24, and tax proteins.
Three proteins (env, gag, and tax) encoded by the human T-cell leukemia virus type I (HTLV-I) genome were cloned and expressed in Escherichia coli. The env protein contained a substantial part of the gp46 domain and a majority of the p21e domain. The gag protein contained all of p24 and portions of p19 and p15. In addition to these two structural proteins, a full-length tax (p40X) construct was obtained. All three recombinant proteins were purified to near homogeneity. When used in an immunoblot assay, the three recombinant proteins detected antibodies in more HTLV-I antibody-positive patient sera than did the corresponding native proteins. Antibodies to at least two of these three different gene products were detected in 98.4% of adult T-cell leukemia patients, 100% of HTLV-I-associated myelopathy patients, 97.4% of asymptomatic carriers, and 94% of uncharacterized HTLV-I-positive patients. Antibody to recombinant tax was found in 4.9% of adult T-cell leukemia patients, whereas antibody to recombinant env could not be detected. These recombinant proteins from three different gene products may be useful in detecting or confirming the presence of antibodies to HTLV-I.
Adult↗