Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies indicate that chronic asthma is associated with a spectrum of glucocorticoid receptor (GCR) binding abnormalities that are cytokine-inducible. These GCR abnormalities may contribute to poor asthma control and failure to respond to glucocorticoid (GC) therapy. The purpose of this study was to determine whether GCR defects are associated with poorly controlled asthma, and whether diminished GCR binding is reversible following a course of GC therapy. We enrolled 12 patients with poorly controlled asthma characterized by nocturnal awakening with cough or wheezing, AM FEV1 < 70%, or FEV1 variability of > 25% requiring a short course of high dose GC therapy. GCR binding affinity was measured in peripheral blood mononuclear cells using a radioligand binding assay before and after the GC course. Spirometry, serum cortisol, eosinophil cationic protein (ECP), and soluble IL-2 receptor (sIL-2R) levels were also performed before and after the GC course. At baseline, all subjects had airflow obstruction that significantly improved (median FEV1 increased from 65.0% to 89.5% of predicted, median FEV1/FVC ratio increased from 0.60 to 0.72) with therapy. A diminished GCR binding affinity at baseline was noted with an elevated median dissociation constant (Kd) of 29.0 nM (interquartile range at the 25th and 75th percentile [IQ] of 22.3 and 44.5 nM) compared with normal controls (Kd 8.0 nM [IQ 7.0, 9.2]). Following the GC course, a significant decrease in the Kd was seen. Serum ECP and sIL-2R levels at baseline were elevated, with serum ECP demonstrating a significant reduction following the GC course.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced glucocorticoid binding affinity in asthma is related to ongoing allergic inflammation. 776 11

Human rhinoviruses (HRVs) cause the common cold and often induce lower airway symptoms such as cough and wheezing. Although HRV infection is presumed to involve primarily ciliated epithelial cells, this has not been confirmed in vivo, and the cellular distribution and spread of infection as well as the pathogenesis of cold related nasal and chest symptoms remain speculative. We have developed in situ hybridization (ISH) to explore localization of the virus to airway tissues, employing HRV 16-derived oligonucleotide probes after sequencing part of the genome of this serotype. A reverse transcription-polymerase chain reaction was used to generate DNA from HRV 16 for sequencing; this yielded 305 nucleotide bases that showed considerable homology to other HRVs. The HRV 16 sequence was used to design oligonucleotides functioning as antisense and sense probes. These probes as well as random sequence and pathogen control oligonucleotides were applied to HRV-infected cell-clot complexes and finally to sections from six paired nasal biopsies obtained before, during, or after HRV-proven colds. Specificity of hybrids was established by the absence of signal in uninfected tissue, in cells infected with other viruses, after RNase pretreatment, and with application of control probes. Hybridization signals were observed in epithelial cells in three of six biopsies obtained during a cold, using probes to viral (+) strand; intermediate (-) strand, implying viral replication, was present in one biopsy. Evidence for infection of nonepithelial cells was inconclusive. HRVs cause productive infection of nasal epithelium during a cold and their intracellular localization may produce perturbation of inflammatory mediators and cytokine profiles.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of rhinovirus infection of the nasal mucosa by oligonucleotide in situ hybridization. 811 Apr 76

Ciliary neurotrophic factor (CNTF) is a neuroactive cytokine found in Schwann cells, which appears to be released in response to nerve injury. The ALS CNTF Treatment Study (ACTS) clinical trial was a phase II-III randomized, placebo-controlled, double-blind study designed to evaluate the safety, tolerability, and efficacy of subcutaneous administration of recombinantly produced human CNTF (rHCNTF) in slowing disease progression in 730 patients with amyotrophic lateral sclerosis (ALS). Patients were randomized to receive 30 micrograms/kg or 15 micrograms/kg rHCNTF or placebo subcutaneously three times a week for 9 months. The primary endpoint of the study, the slope of decline of isometric muscle strength in treated versus placebo patients, showed no statistically significant difference between rHCNTF and placebo-treated patients, and was complicated by an initial statistically significant decrease in strength early in rHCNTF-treated patients. Mortality was similar in all three study arms. There were no statistically significant treatment effects among the secondary measures. Side effects of rHCNTF included anorexia, weight loss, and cough and were sufficient to limit dosing in many patients.
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PMID:A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. ALS CNTF Treatment Study Group. 862 60

Fifty-seven patients with amyotrophic lateral sclerosis (ALS) were randomly assigned to receive 0.5, 1, 3, 7, 10, or 30 micrograms/kg recombinant human ciliary neurotrophic factor (rHCNTF) or placebo subcutaneously 3 times a week for 2 weeks. Dose-limiting toxicity, consisting of febrile reactions in some patients, fatigue, and nonproductive cough, was observed at a dose level of 30 micrograms/kg. Dose-related changes in parameters of the acute-phase response were noted, consistent with the relationship of CNTF and its receptor system to the cytokine interleukin-6 (IL-6) and its receptor. No adverse neurologic consequences of rHCNTF administration were observed. Antibodies to rHCNTF were observed in sera of most patients tested after 2 weeks of continuous treatment and 4 weeks' withdrawal period. rHCNTF was safe and tolerated within acceptable limits when administered to patients with ALS in this study at doses of up to 30 micrograms/kg 3 times a week for 2 weeks. Further studies to explore the efficacy of rHCNTF in the treatment of human motor neuron diseases are justified.
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PMID:A phase I study of recombinant human ciliary neurotrophic factor (rHCNTF) in patients with amyotrophic lateral sclerosis. The ALS CNTF Treatment Study (ACTS) Phase I-II Study Group. 868 12

One hundred patients operated for left atrial myxoma in the same surgical department underwent clinical and anatomical assessment at long-term from 1959 to July 1995 (66 women and 34 men, average age 52.2 years). The clinical presentation was related to mitral valve obstruction in half the cases (dyspnoea, cough, pulmonary oedema), the presentation in the other half of cases being very variable. The widespread use of echocardiography has relegated other investigations to a subsidiary role: auscultation, radiology, ECG (9 cases diagnosed by echocardiography performed for another indication). Serious complications of left atrial myxoma include systemic embolism : 37 cases out of the 100 in this series, including 10 plurifocal but mainly cerebral (19 cases including 11 isolated cerebral emboli). Surgical treatment is well established, should not be deferred and gives excellent results (2 early postoperative deaths out of 100 cases in the early years of the study). There were 6 cases of recurrences including 3 cases of Carney's syndrome. Clinico-pathological correlations showed that mitral stenotic effects occurred when the tumour diameter exceeded 5 cm and embolism was associated with tumours having multiple villositi. Histopathological analysis distinguished between active and inactive tumours, differentiated or not, and enabled the elaboration of hypotheses on the rate of growth of the tumour and on the absence of true metastases. Histopathological techniques also show the presence of lymphoplasmocytic infiltration, the sign of secretion of interleukin 6 by the myxoma, a cytokine involved in the general inflammatory process and which explains the unusual clinical presentation sometimes observed.
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PMID:[Myxoma of the left atrium, Clinical outcome of 100 operated patients]. 895 35

Transforming growth factor-beta (TGF-beta) is a cytokine that promotes extracellular matrix accumulation and inhibits matrix degradation. Although the natural course of sarcoidosis is usually favourable, granuloma healing in the lung may result in pulmonary fibrosis and respiratory impairment in some patients. In this study TGF-beta1 was evaluated in bronchoalveolar lavage (BAL) fluid and culture supernatants of alveolar macrophages (AM) from 73 patients with biopsy-proven sarcoidosis. Disease activity was defined when patients recently developed or increased symptoms (cough, dyspnoea, systemic symptoms) and/or demonstrated increasing opacities on chest radiography. Pulmonary function tests were performed in all patients including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), total lung capacity (TLC) and the diffusing capacity of the lung for carbon monoxide (DL,CO). Fourteen patients with idiopathic pulmonary fibrosis (IPF) and 14 healthy subjects were investigated as a control group. Immunohistochemistry was used to evaluate the cell distribution of TGF-beta1 on lung specimens. TGF-beta1 levels in BAL and in AM supernatants were not different between sarcoidosis and healthy subjects, whereas they were markedly increased in IPF. However, the TGF-beta1 level was significantly increased in BAL fluid but not in AM supernatants from sarcoidosis with altered lung function, compared with patients with normal lung function. The TGF-beta1 level in BAL was increased in active sarcoidosis but this increased level was mainly related to the higher level observed in patients with altered lung function. TGF-beta1 levels in BAL correlated significantly with the lymphocyte percentage. TGF-beta1 staining assessed by immunohistochemistry was intense in epithelioid histiocytes comprising non-necrotizing granuloma and in bronchiolar epithelial cells, in hyperplastic type II pneumocytes and occasionally in AM. This study supports the hypothesis that overproduction of transforming growth factor-beta1 is associated with functional impairment in patients with pulmonary sarcoidosis.
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PMID:Transforming growth factor-beta1 in sarcoidosis. 981 68

Cell-mediated immune (CMI) responses to Bordetella pertussis antigens (pertussis toxin [PT], pertactin [PRN], and filamentous hemagglutinin [FHA]) were assessed in 48-month-old recipients of acellular pertussis [aP] vaccines (either from Chiron-Biocine [aP-CB] or from SmithKline Beecham [aP-SB]) and compared to CMI responses to the same antigens at 7 months of age, i.e., 1 month after completion of the primary immunization cycle. None of the children enrolled in this study received any booster of pertussis vaccines or was affected by pertussis during the whole follow-up period. Overall, around 75% of 4-year-old children showed a CMI-positive response to at least one B. pertussis antigen, independently of the type of aP vaccine received, and the proportion of CMI responders were at least equal at 48 and 7 months of age. However, longitudinal examination of individual responses showed that from 20 (against PT) to 37% (against FHA) of CMI responders after primary immunization became negative at 48 months of age. This loss was more than compensated for by conversion to positive CMI responses, ranging from 36% against FHA to 69% against PRN, in other children who were CMI negative at 7 months of age. In 60 to 80% of these CMI converters, a lack of decline or even marked elevation of antibody (Ab) titers against B. pertussis antigens also occurred between 20 and 48 months of age. In particular, the frequency of seropositivity to PRN and FHA (but not to PT) was roughly three times higher in CMI converters than in nonconverters. The acquisition of CMI response to B. pertussis antigens in 48-month-old children was not associated with a greater frequency of coughing episodes lasting >/=7 days and was characterized by a prevalent type 1 cytokine profile, with high gamma interferon and low or no production of interleukin-5, reminiscent of cytokine patterns following immunization with whole-cell pertussis vaccine or natural infection. Our data imply that vaccination-induced systemic CMI may wane by 4 years of age but may be acquired or naturally boosted by symptomless or minor clinical infection by B. pertussis. This might explain, at least in part, the persistence of protection against typical pertussis in aP vaccine recipients despite a substantial waning of both Ab and CMI responses induced by the primary immunization.
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PMID:Cell-mediated immune responses in four-year-old children after primary immunization with acellular pertussis vaccines. 1041 75

We have previously described that in bronchoalveolar lavage fluid (BALF), eosinophils characterize asthma and neutrophils are more prominent in infantile wheeze. In this study, we hypothesized that intercellular adhesion molecule 1 (ICAM-1) and interferon-gamma (IFN-gamma) would have a role in promoting migration of both cell types into the airway. To investigate this, we measured soluble (s) ICAM-1 in 68 BALFs from infants and young children with various respiratory problems. Children with asthma were characterized by significantly raised sICAM compared with those with chronic cough without wheeze (p = 0.05) or control subjects with no lower airway pathology (p = 0.045). The levels correlated with disease severity (evaluated with a symptom score) and with lymphocyte numbers. IFN-gamma levels were also raised in children with asthma compared with those with chronic cough (p = 0.05), but there was no correlation with disease activity. Infantile wheeze was characterized by a linear correlation between sICAM-1 and IFN-gamma (r = 0.55; p = 0.002). sICAM-1 levels in infantile wheeze correlated with the severity of the disease and lymphocyte numbers. IFN-gamma levels were elevated in the wheezers treated with inhaled steroids compared with untreated infants (p = 0.03). Although sICAM-1 levels were increased in those with severe cough, no characteristic inflammatory profile was found in the group with chronic cough. Our study suggests that ICAM-1 and IFN-gamma play a role in the activity of the inflammatory process in asthma in childhood and possibly in some infant wheezers, in whom IFN-gamma may be one of the factors increasing the expression of ICAM-1. The role of IFN-gamma, a T helper-1 cytokine, in children with asthma remains to be fully understood.
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PMID:Soluble intercellular adhesion molecule-1 (sICAM-1) and interferon-gamma in bronchoalveolar lavage fluid from children with airway diseases. 1098 23

A 15-year-old girl, high school student, became febrile (38-39 degrees C) with chills, sore throat and cough on April 20, 1994. Until the onset, she was healthy and she had been camping with her classmates in a wooded mountainous area in Oku-etsu, Fukui Prefecture. She consulted a local clinic on April 21 and bacampicillin was initially administered and then changed to cefaclor on April 23. However, high body temperature continued and a maclopapular rash appeared on her face on April 24 and gradually spread to her anterior chest and back. Blood examination showed a WBC count of 2,200/microliter, and she was admitted to our hospital on April 25. On admission, peripheral blood data showed leukocytopenia (WBC 2,300/microliter) with 5% atypical lymphocytes. Titers of anti-Rickettsia typhi serum antibodies (IgM, -G) were elevated (1:80, 1:640) and she was diagnosed as having murine typhus. On the second hospital day, 200 mg of minocycline (MINO) was administered per os and her body temperature fell to within the normal limits on the third hospital day. On the 7th hospital day, the skin rash disappeared and she was discharged. Altogether, 320 high school students went camping with this patient. Among them, approximately 30 students had similar symptoms and signs as this case and had been diagnosed suspected viral infection. Twelve students of the 30 were admitted to other hospitals. It was considered that this case was part of an outbreak of murine typhus in the Oku-etsu area, Fukui Prefecture, but no further investigation was performed. Murine typhus is usually a benign disease that is controllable by the administration of MINO. In rare cases, infection can worsen to multiorganic failure, severe complications have been reported in 1-4% of cases, and death has been reported in less than 3%. Recently, it has also been reported that MINO not only has an antibiotic effect, but also play acts as a cytokine modulator in patients with rickettsial infection. Thus, in febrile patients in whom uncommon Rickettsia infection is suspected, serological test for murine typhus should be examined and the immediate administration of MINO is important.
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PMID:[Murine typhus infected in Oku-etsu area, Fukui Prefecture]. 1135 25

Mycoplasma hyopneumoniae (Mh) is the primary infectious pathogen responsible for enzootic pneumonia in pigs. Although Mh is thought to impair growth performance, whole-body composition, and fat and protein accretion in pigs with pneumonia have not been reported and the mechanism through which Mh reduces growth is unknown. The objectives of this study were to evaluate the effects of Mh on growth performance, whole-body composition, and protein and fat accretion in nursery pigs and to determine whether Mh infection increases the expression of interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha). Sixty-four 2-wk-old Mh-free pigs were used (two trials) in a randomized complete block design. In each trial, two pigs were housed in each of 16 disease-containment chambers. At 4 wk of age, pigs were inoculated intratracheally with 3 mL of Mh broth (P5722-3, 10(7) cfu/mL) or sterile Friis culture medium. Clinical signs of disease and feed intake were monitored daily and body weight was determined weekly for 4 wk. Whole-body composition was determined from pigs killed 0, 14, and 28 d after inoculation, and the comparative slaughter technique was used to estimate protein and fat accretion. At death, gross lung lesions were quantified, and lung tissue was collected to verify the presence or absence of Mh, and to determine cytokine mRNA levels. Control pigs displayed no overt signs of infection and were Mh-negative and free of pulmonary lesions. Pigs inoculated with Mh showed pneumonic coughing (P < 0.005), were Mh-positive, and had pulmonary lesions that affected 4.5% (P < 0.01) and 14.1% (P < 0.001) of total lung surface area at 14 and 28 d, respectively, after inoculation. Ribonuclease protection assays revealed increased IL-1beta (P < 0.04) and TNF-alpha (P < 0.06) mRNA in lung tissue collected from a lesion site compared with tissue collected 10 cm from a lesion site or from control pigs. Interestingly, Mh did not depress weight gain or feed efficiency during any week of the 28-d study (P > 0.10). Moreover, Mh did not affect whole-body fat or protein accretion (P > 0.10). Thus, in spite of inducing disease and expression of inflammatory cytokines, Mh alone did not affect growth performance and whole-body composition of nursery pigs during the 4-wk experiment. The ability of pigs to contend with Mh may have resulted from the absence of other pathogens that generally co-exist with Mh under commercial conditions.
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PMID:Growth performance and whole-body composition of pigs experimentally infected with Mycoplasma hyopneumoniae. 1188 29


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