PubMed Health⌕ Search

Biomedical subjects

M J Mäkelä

Publications and source records attributed to M J Mäkelä.

At least 19 recordsLinked to original sources
PubMed2006

Exhaled nitric oxide in healthy nonatopic school-age children: determinants and height-adjusted reference values.

Exhaled nitric oxide (FENO) was proposed as a marker of airway inflammation, but data about FENO in healthy children measured with standardized methods are so far limited. In order to assess the determinants of FENO in healthy children, we investigated a population-based sample of school-age children (n = 276) with a questionnaire, skin-prick tests, spirometry, and the measurement of FENO. The FENO of 114 nonatopic and nonsmoking children considered healthy were analyzed with stepwise multiple regression analysis, which showed significant associations with age, standing height, weight, and body surface area, but not with gender. Height was found to be the best independent variable for the regression equation for FENO, which on average showed an increase in the height range of 120-180 cm from 7 to 14 ppb. In the random sample of children, increased FENO was associated with atopy (odds ratio, 9.0; 95% confidence interval, 3.9-21.1; P < 0.0001), and significantly with allergic rhinitis and atopic dermatitis, but not with asthma. Respiratory symptom-free children with skin-prick test positivity had significantly higher FENO than healthy nonatopic subjects. We conclude that height is the best determinant of FENO in healthy children. Due to the strong effect of atopy, FENO data should not be interpreted without knowing the atopic status of the child. The present reference values of FENO may serve in clinical assessments for measuring airway inflammation in children.

Adolescent↗
PubMed2003

In vitro kinetics of allergen- and microbe-induced IL-4 and IFN-gamma mRNA expression in PBMC of pollen-allergic patients.

BACKGROUND: According to a hypothesis allergens induce Th2 responses in allergic patients, and microbes induce Th1 responses. We studied the kinetics of in vitro allergen-, tuberculin (PPD)- and tetanus toxin (TT)-induced IFN-gamma and IL-4 mRNA expression in peripheral blood mononuclear cell (PBMC) cultures of pollen-allergic patients and healthy controls. METHODS: PBMC of 10 birch or timothy pollen-allergic patients and of 13 healthy controls were stimulated in vitro with allergen (birch or timothy), PPD or TT. Pellets and supernatants were collected at 24, 48, 72 and 96 h after stimulation. IFN-gamma and IL-4 production was measured by enzyme linked immunosorbent assay and mRNA expression using RT-PCR and time-resolved fluorometry. RESULTS: Allergen induced IFN-gamma production and mRNA expression in PBMC more in allergic patients than in healthy controls. Also allergen induced IL-4 mRNA expression more in allergic patients than in healthy controls. PPD induced IFN-gamma mRNA expression both in allergic patients and healthy controls, whereas IFN-gamma production was induced only in healthy controls and IL-4 was not induced at all. TT induced IFN-gamma mRNA expression in both groups, IFN-gamma production in allergic patients, and IL-4 mRNA expression in both allergic patients and healthy controls. CONCLUSIONS: In vitro stimulation with allergen induced both IFN-gamma and IL-4 mRNA expression of PBMC in allergic patients. These observations challenge the clearcut division of microbe-specific Th1 and allergen-specific Th2 responses in peripheral blood.

Adult↗
PubMed2001

Tumor necrosis factor-alpha negatively regulates airway hyperresponsiveness through gamma-delta T cells.

Tumor necrosis factor (TNF)-alpha is a potent cytokine with immunomodulatory, proinflammatory, and pathobiologic activities. Although TNF-alpha is thought to play a role in mediating airway inflammation and airway hyperresponsiveness (AHR), its function is not well defined. TNF-alpha-deficient mice and mice expressing TNF-alpha in their lungs because of a TNF-alpha transgene placed under the control of the surfactant protein (SP)-C promoter (SP-C/TNF-alpha-transgenic mice) were sensitized to ovalbumin (OVA) and subsequently challenged with OVA via the airways; airway function in response to inhaled methacholine was monitored. In the TNF-alpha-deficient mice, AHR was significantly increased over that in controls. In contrast, the transgenic mice failed to develop AHR. In addition, sensitized/ challenged TNF-alpha-deficient mice had significantly increased numbers of eosinophils and higher levels of interleukin (IL)-5 and IL-10 in their bronchoalveolar lavage fluid than were found for control mice. However, in SP-C/TNF-alpha-transgenic mice, both the numbers of eosinophils and levels of IL-5 and IL-10 were significantly lower than in sensitized/challenged transgene-negative mice. gammadelta T cells have been shown to be activated by TNF-alpha and to negatively regulate AHR. Depletion of gammadelta T cells in the TNF-alpha-transgenic mice in the present study increased AHR, whereas depletion of these cells had no significant effect in TNF-alpha-deficient mice. These data indicate that TNF-alpha can negatively modulate airway responsiveness, controlling airway function in allergen-induced AHR through the activation of gammadelta T cells.

Allergens↗
PubMed2001

Inhibition of phosphodiesterase 4 attenuates airway hyperresponsiveness and airway inflammation in a model of secondary allergen challenge.

We compared for the first time the therapeutic potential of a specific phosphodiesterase 4 (PDE4) inhibitor, rolipram, with anti-VLA-4 and anti-IL-5 in a model of secondary allergen exposure of previously sensitized and challenged mice. To address these issues, mice were sensitized and challenged with ovalbumin (OVA) (primary challenge). Six weeks later, sensitized/challenged mice were reexposed to OVA (secondary challenge) and airway response (resistance [RL] and dynamic compliance [Cdyn]) to inhaled methacholine was monitored. After secondary OVA challenge, RL significantly increased as did the number of lung inflammatory cells and IL-4 and IL-5 production in bronchoalveolar lavage fluid (BALF). Administration of rolipram, in a dose-dependent manner, significantly prevented both changes in RL and Cdyn, as well as eosinophil, lymphocyte, and neutrophil accumulation in the BALF; IL-4 and IL-5 levels in BALF were also significantly reduced. In contrast, treatment with anti-VLA-4 and anti-IL-5 only prevented changes in RL and eosinophil numbers and IL-5 production in BALF. Further, goblet cell hyperplasia was suppressed only by treatment with rolipram. None of the treatments affected OVA-specific antibody levels. These studies confirm that IL-5 dependent eosinophilic inflammation plays an essential role in the development of certain aspects of airway function after rechallenge of sensitized mice and that lymphocytes and neutrophils are also important in the development of altered airway function. The use of agents that inhibit PDE4 may have an important role in the treatment of asthma in previously sensitized mice.

Airway Resistance↗
PubMed2000

IL-10 is necessary for the expression of airway hyperresponsiveness but not pulmonary inflammation after allergic sensitization.

Cytokines play an important role in modulating inflammatory responses and, as a result, airway tone. IL-10 is a regulatory cytokine that has been suggested for treatment of asthma because of its immunosuppressive and anti-inflammatory properties. In contrast to these suggestions, we demonstrate in a model of allergic sensitization that mice deficient in IL-10 (IL-10-/-) develop a pulmonary inflammatory response but fail to exhibit airway hyperresponsiveness in both in vitro and in vivo assessments of lung function. Reconstitution of these deficient mice with the IL-10 gene fully restores development of airway hyperresponsiveness comparable to control mice. These results identify an important role of IL-10, downstream of the inflammatory cascade, in regulating the tone of the airways after allergic sensitization and challenge.

Aerosols↗
PubMed2000

Validity of ultrasonography in diagnosis of acute maxillary sinusitis.

BACKGROUND: Accurate diagnosis of maxillary sinusitis is difficult on the basis of clinical examination only because the signs and symptoms of sinusitis are nonspecific. A simple, rapid, and readily available method for diagnosing maxillary sinusitis in primary care would increase the accuracy of the diagnoses and thus reduce unnecessary antibiotic treatment. OBJECTIVE: To investigate the validity of ultrasonography compared with radiography and magnetic resonance imaging (MRI) in detection of maxillary sinusitis. DESIGN: Ultrasonography and plain-film radiography of the paranasal sinuses were performed on all patients and MRI was performed on 40 randomly selected patients on day 7 of the study. SETTING: Study office at the Department of Pediatrics of Turku University Hospital, Turku, Finland. PATIENTS: One hundred ninety-seven young adults who contacted the study office within 48 hours of the onset of symptoms of the common cold. MAIN OUTCOME MEASURES: Detection rates of maxillary sinusitis by ultrasonography, radiography, and MRI. RESULTS: Acute maxillary sinusitis was diagnosed in 24% of the sinuses by radiography and in 28% by MRI. Compared with MRI findings, the sensitivity of ultrasonography for detection of maxillary sinusitis was 64% (specificity, 95%). Using a 2-step diagnostic approach in which radiological findings were additionally considered in cases of negative ultrasound findings, a sensitivity of 86% (specificity, 95%) was observed. CONCLUSIONS: The high specificity of ultrasonography indicates that a positive ultrasound finding can be regarded as evidence of maxillary sinusitis. The addition of plain-film radiography in cases of negative ultrasound findings increases the diagnostic sensitivity to clinically acceptable levels without loss in specificity. Active use of ultrasonography would substantially decrease the need for radiological imaging of the sinuses and also help reduce unnecessary antibiotic treatment in primary care. Arch Otolaryngol Head Neck Surg. 2000;126:1482-1486

Acute Disease↗
PubMed2000

Clinical efficacy and safety of the orally inhaled neuraminidase inhibitor zanamivir in the treatment of influenza: a randomized, double-blind, placebo-controlled European study.

OBJECTIVES: To assess the clinical efficacy and safety of orally inhaled zanamivir in the treatment of influenza in a European primary care setting. METHODS: This was a randomized, double-blind, placebo-controlled trial in primary care and hospital clinics in 11 European countries. Patients aged > or = 12 years were recruited within 2 days of onset of typical influenza symptoms and received orally inhaled zanamivir 10 mg via a Diskhaler twice daily for 5 days or matching placebo. Influenza symptoms and temperature were recorded daily for 14 days. The primary endpoint was time to alleviation of clinically significant symptoms of influenza. Other endpoints included symptom severity, use of relief medications, time to return to normal activities, complications and investigator's assessment of symptoms. RESULTS: A total of 356 patients were recruited; 277 (78%) had laboratory-confirmed influenza and 32 (9%) were considered high-risk (i.e. elderly or with underlying medical conditions). Zanamivir significantly reduced the time to alleviation of symptoms versus placebo (median 5 days versus 7.5 days, P<0.001), a 33% reduction in duration of illness. Zanamivir significantly reduced the severity of several symptoms; improvements versus placebo were discernible after approximately 24 h. The proportion of patients who were afebrile after 24 h increased by 46% versus placebo. Similar treatment benefits were observed in the high-risk patients. Zanamivir was well tolerated, with an adverse event profile similar to that of placebo. CONCLUSIONS: Zanamivir is effective in reducing the duration and severity of influenza illness and is well tolerated. Zanamivir should therefore be a clinically valuable intervention in the management of influenza.

Adolescent↗
PubMed2000

Critical roles for interleukin-4 and interleukin-5 during respiratory syncytial virus infection in the development of airway hyperresponsiveness after airway sensitization.

In mice, respiratory syncytial virus (RSV) infection can enhance the consequences of allergic airway sensitization, resulting in lung eosinophilia and the development of airway hyperresponsiveness (AHR) to inhaled methacholine (MCh). To delineate a role for interleukin-5 (IL-5), interleukin-4 (IL-4), and interferon gamma (IFN-gamma) in mediating the effects of RSV infection on subsequent allergic sensitization, we treated BALB/c mice with anti-IL-5 during acute RSV infection but not during subsequent exposure to ovalbumin (OVA). IL-5-deficient and IL-4-deficient mice were also treated with IL-5 either during acute RSV infection or during the sensitization period. Airway responsiveness to inhaled MCh was assessed and numbers of lung eosinophils were monitored. Anti-IL-5 treatment during RSV infection reduced AHR and lung eosinophilia after subsequent exposure to allergen. In IL-5-deficient or IL-4-deficient mice lung eosinophilia and AHR after RSV infection and allergen exposure were also markedly reduced. IL-5 administration during RSV infection restored the responses to allergen in both IL-5- and IL-4-deficient mice. However, IL-5 administration only during sensitization restored these responses in IL-4-deficient but not in IL-5-deficient animals. IFN-gamma-deficient mice developed AHR and some lung eosinophilia after allergen exposure alone and when RSV infection preceded allergen, these responses were enhanced. We conclude that both IL-5, particularly during acute infection, and IL-4 are critical in mediating the effects of RSV infection on allergic airway sensitization, resulting in the development of AHR and lung eosinophilia.

Animals↗
PubMed1999

Simultaneous detection of IFN-gamma and IL-4 mRNAs using RT-PCR and time-resolved fluorometry.

Time-resolved fluorometry was applied in the detection of RT-PCR amplified mRNAs for the Th1 and Th2 cell-derived cytokines interferon gamma (IFN-gamma) and interleukin (IL-)4, respectively. RNA stimulated cells was reverse transcribed and the cDNAs for the cytokine mRNAs and the constantly expressed beta-actin (beta-ACT) mRNA were simultaneously amplified in one multiplex PCR reaction. The PCR conditions were optimized to minimize mutual inhibition of individual amplifications. One of the PCR primers in each primer pair was biotinylated, and the PCR products were captured onto streptavidin-coated microtitre plates. The three PCR products were detected with three different lanthanide labelled target-specific probes in solution hybridization. IFN-gamma, IL-4 and beta-ACT were detected with europium (Eu), terbium (Tb) and samarium (Sm) labelled probes, respectively, using time-resolved fluorometry. Small cell numbers used in microtitre plate cultures were sufficient to detect cytokine messages after mitogen stimulation. This sequence-based method provides a sensitive, specific, fast and nonisotopic alternative to conventional blotting and hybridisation with radioactive probes. In addition, the multiplex fluorogenic dye detection facilitates relative quantification of target mRNAs.

Actins↗
PubMed1999

Lack of induction by rhinoviruses of systemic type I interferon production or enhanced MxA protein expression during the common cold.

To study whether MxA protein expression is systemically upregulated during rhinovirus infection, blood specimens were collected from 40 patients with common cold and MxA expression in mononuclear cells analyzed by flow cytometry. None of the patients with a confirmed rhinovirus infection (n = 15) or with an infection of unknown etiology (n = 20) had elevated expression of the MxA protein (median fluorescence intensity, 549 and 582, respectively) when compared to healthy controls (n = 11, median 590). Patients with influenza infections had significantly elevated values (n = 5, median 750), and interferon could be detected only in serum samples from influenza patients. In conclusion, expression of MxA in blood lymphocytes and an apparently systemic type I interferon response is not induced during rhinovirus infection or during most other cases of common cold in young adult patients.

Adult↗
PubMed1999

Effects of the common cold and intranasal fluticasone propionate treatment on mucosal host defense assessed by human saliva.

OBJECTIVE: The purpose of this investigation was to study the effect of a potent topical steroid, fluticasone propionate, on patients with early signs and symptoms of the common cold. To characterize the mucosal inflammatory response, salivary defense factors and flow rate in these patients were analyzed. STUDY DESIGN: Forty patients with symptoms of the common cold were randomized into 2 groups to receive either high-dose fluticasone propionate (100 microg per nostril) or placebo 4 times daily for 6 days. Paraffin-stimulated whole saliva was collected on day 1 (before the onset of medication), day 7 (posttreatment), and day 21 (follow-up). RESULTS: Salivary flow rate, innate host defense factors, and total protein content were not affected by the common cold. IgA increased between day 7 and day 21 (P < or = .01; Student 2-tailed t test), and the relative proportions of salivary peroxidase and IgA increased on day 7 (P = .01) and day 21 (P= .05). In patients receiving fluticasone, saliva flow rate was lower on day 21 (P < or = .05) than on days 1 and 7. The innate salivary defense factors were not affected, but IgA increased both on day 7 (P < or = .001) and on day 21 (P < or = .001) in comparison with day 1. CONCLUSIONS: Of the oral mucosal defense factors, only IgA is activated during the common cold. Intranasally administrated fluticasone propionate does not have a suppressive effect on salivary antimicrobial capacity.

Administration, Intranasal↗
PubMed1998

Sinusitis in the common cold.

BACKGROUND: Acute community-acquired sinusitis is considered a bacterial complication of the common cold. Radiologic abnormalities in sinuses occur, however, in most patients with upper respiratory virus infections. OBJECTIVE: Assessment of the occurrence, clinical profile, laboratory findings, and outcome of radiologically confirmed sinusitis was carried out as part of a common cold study in young adults. METHODS: Clinical examinations and radiography of the paranasal sinuses were carried out on days 1, 7, and 21 in 197 patients with the common cold. The symptoms were recorded on diary cards on days 1 to 20. Ten viruses and 5 bacteria were studied as etiologic agents of common cold as reported earlier. Serum C reactive protein concentrations, erythrocyte sedimentation rates, and total white blood cell counts with differentials were determined in 40 randomized subjects on day 7. The effect of 6 days of intranasal fluticasone propionate treatment of the common cold in the prevention of sinusitis was analyzed. RESULTS: On day 7, 39% of patients with the common cold in the placebo group (n = 98) had sinusitis, which we would prefer to call viral sinusitis. The symptoms of patients with sinusitis and those without it were not clinically distinguishable. Viral infection was detected in 81.6% of patients with sinusitis. No significantly increased levels of antibodies to bacteria were detected. Serum C reactive protein concentrations, erythrocyte sedimentation rates, and white blood cell counts were low in patients with sinusitis. All patients made a clinical recovery within 21 days without antibiotic treatment. Fluticasone propionate treatment tended to prevent paranasal sinusitis, especially in rhinovirus-positive subjects. CONCLUSION: Viral sinusitis frequently occurs in the early days of the common cold, but it is a self-limited illness. The sinuses should not be imaged in patients with the common cold if the signs and symptoms of illness gradually become less severe and no specific signs suggestive of bacterial sinusitis occur.

Adult↗
PubMed1998

The common cold: effects of intranasal fluticasone propionate treatment.

OBJECTIVE: A double-blind, randomized, placebo-controlled trial was conducted to study the effect of the intranasal corticosteroid, fluticasone propionate (FP), in the naturally occurring common cold. METHODS: One hundred ninety-nine young adults received high-dose FP (200 microg four times daily) or placebo beginning 24 to 48 hours after onset of the common cold for 6 days. All symptoms were recorded on diary cards on days 1 to 20, and clinical examinations were carried out on days 1, 7, and 21. Nasopharyngeal aspirates were collected on days 1 and 7 for detection of rhinoviruses (found in 105 subjects) and Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis (found in 52 subjects) in the nasopharynx. RESULTS: In general, FP treatment had no clinically recognizable effects on the symptoms of the common cold, although it significantly reduced nasal congestion and cough on some study days. After treatment, rhinoviruses were cultured more often in the FP treatment group (37% vs 14%, p < 0.001), but this had no effect on the symptoms of common cold. FP treatment produced no changes in the colonization of pathogenic bacteria in the nasopharynx. Some symptoms of common cold were significantly more severe during days 1 to 10 (p < 0.05) in subjects found to have positive cultures for S. pneumoniae, H. influenzae, or M. catarrhalis in the nasopharynx on day 1 (n = 33). CONCLUSION: FP treatment does not have any marked effects on the symptoms of the common cold. FP treatment induced prolonged shedding of viable rhinoviruses. Some symptoms of the common cold were significantly more severe in subjects with pathogenic bacteria in the nasopharynx.

Administration, Intranasal↗
PubMed1998

Viruses and bacteria in the etiology of the common cold.

Two hundred young adults with common colds were studied during a 10-month period. Virus culture, antigen detection, PCR, and serology with paired samples were used to identify the infection. Viral etiology was established for 138 of the 200 patients (69%). Rhinoviruses were detected in 105 patients, coronavirus OC43 or 229E infection was detected in 17, influenza A or B virus was detected in 12, and single infections with parainfluenza virus, respiratory syncytial virus, adenovirus, and enterovirus were found in 14 patients. Evidence for bacterial infection was found in seven patients. Four patients had a rise in antibodies against Chlamydia pneumoniae, one had a rise in antibodies against Haemophilus influenzae, one had a rise in antibodies against Streptococcus pneumoniae, and one had immunoglobulin M antibodies against Mycoplasma pneumoniae. The results show that although approximately 50% of episodes of the common cold were caused by rhinoviruses, the etiology can vary depending on the epidemiological situation with regard to circulating viruses. Bacterial infections were rare, supporting the concept that the common cold is almost exclusively a viral disease.

Adenovirus Infections, Human↗
PubMed1997

Enhanced spontaneous antibody response after coronary artery bypass surgery.

PURPOSE: Cells spontaneously secreting immunoglobulins can be seen in the blood one week after open-heart surgery. The purpose of this study was to measure the antibody specificities of activated cells. METHODS: Immune responses were studied preoperatively and on the seventh postoperative day in 18 patients undergoing elective coronary artery bypass surgery. The number of cells secreting adenovirus, measles, rubella and tetanus antigen specific antibodies spontaneously and induced by pokeweed mitogen PWM (ASCs) as well as the total number of cells secreting IgG, IgM and IgA (ISCs) were studied using an enzyme-linked immunospot (ELISPOT) assay. Spontaneous as well as phytohaemagglutinin (PHA)- and pokeweed mitogen (PWM)-induced lymphocyte proliferation was also measured. RESULTS: The number of cells spontaneously secreting IgG, IgM and IgA antibodies was increased on the seventh day after coronary bypass surgery, against adenovirus, measles, rubella and tetanus as well as the total number of cells secreting immunoglobulins IgG, IgM and IgA (P < 0.05/0.001). By contrast, only slight fluctuation was seen in the numbers of cells secreting antibodies after PWM stimulation. Spontaneous lymphocyte proliferation was also increased, PHA proliferative responses were depressed and PWM responses were not changed on the seventh postoperative day compared with preoperative values. CONCLUSION: Coronary artery bypass surgery caused marked polyclonal B cell activation demonstrated by an increase of cells producing spontaneously antibodies against virus antigens and tetanus toxoid. This activation could not be intensified by PWM stimulation.

Adult↗
PubMed1997

Expression of MxA protein in blood lymphocytes discriminates between viral and bacterial infections in febrile children.

Interferons (IFNs), which are induced by viruses, form an essential part of host's defense systems against viral infections. The antiviral actions of IFNs are mediated by several IFN-inducible gene products, one of which is Mx protein. To evaluate whether MxA protein expression in lymphocytes could function as an indicator of endogenous IFN production in children with acute febrile illness, we analyzed MxA protein levels in peripheral blood lymphocytes by flow cytometry in the acute phase of the disease. Children with a laboratory-confirmed viral infection [respiratory syncytial virus (RSV) in 21, adenovirus in 10, rotavirus in 5, and influenza, herpes simplex, or EBV in 7 other cases] had significantly higher (p < 0.002) MxA protein levels (median fluorescences in different virus groups ranged from 707 to 765) compared with children with a bacterial infection (n = 12, median fluorescence 548). To characterize further MxA protein expression during infections, cells from 41 patients were stimulated in vitro with exogenous IFN-alpha, and the level of MxA protein expression was determined. The rise in MxA staining levels was significantly higher in the group with bacterial infections compared with those with viral infection (p < 0.005), further indicating that the MxA protein levels were already elevated in vivo in patients with viral infections. This study suggests that elevated MxA protein expression levels can be used in the differential diagnosis of bacterial versus viral disease in febrile children.

Adenoviridae Infections↗
PubMed1995

Virus-specific, antibody-secreting cells during upper respiratory infections.

The humoral immune response of 18 army recruits with febrile upper respiratory infection (URI) was studied by enumerating virus-specific, antibody-secreting cells in the peripheral blood. Diagnosis was based on viral antigen detection in nasopharyngeal specimens, virus isolation from throat swabs, or on antibody measurement from paired serum samples. At the time of the sample collection, three viruses, including adenovirus, influenza A, and influenza B, were found mainly to cause URIs among the recruits, and ELISPOT assay for enumeration of the specific antibody-secreting cells was selected for these viruses. Of the 36 patients with febrile URI studied, viral diagnosis was made in 18 cases, which included 11 patients with adenovirus infection, three with influenza A, and four with influenza B. The first blood sample was collected at the first signs of URI and the second and third samples at 2-week intervals. The adenovirus-positive patients developed a strong IgG class antibody-secreting cell response against the homologous virus, which peaked at the first sample and decreased steeply by the second and third samples. In the influenza A and B patients, the response was similar kinetically to that seen in adenovirus-positive patients. In those cases where also IgA and IgM class antibody-secreting cells were determined, the IgG response dominated. The ELISPOT method has potential also as a diagnostic tool for respiratory infections.

Adenovirus Infections, Human↗