bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neonatal Thyroid-Stimulating Hormone Screening as an Indirect Method for the Assessment of Iodine Deficiency in Estonia
Authors: Mikelsaar Ruth V. , Viikmaa Mart 
Published: April 2003

According to neonatal thyroid screening the incidence of congenital hypothyroidism in Estonia is 1:2,860. Transient hyperthyrotropinemia with a raised thyroid-stimulating hormone level of 5 μU/ml occurred in 17.7% of infants and was not associated with low birth weight, small birth length, low gestational age or congenital anomalies. Based on WHO criteria (WHO/UNICEF, 1994) it corresponds to mild iodine deficiency in Estonia (3% or less is in iodine-sufficient areas). This is in agreement with the previously reported median urinary iodine content of 65 μg/l in children. The frequency of infants with TSH >5 μU/ml was 16.4, 21 and 17.2% in three regions (north, central and south) of Estonia, respectively, indicating mild to moderate iodine deficiency. These findings show the possibility of using the results of newborn screening for congenital hypothyroidism to assess the severity of iodine deficiency in Estonia. The introduction of universal iodine prophylaxis is recommended.
Effect of Growth Hormone and Oxandrolone Treatment on Glucose Metabolism in Turner Syndrome
Authors: Joss E.E. , Zurbrügg R.P. , Tönz O. , Mullis P.-E. 
Published: April 2003

In 18 girls with Turner syndrome, glucose tolerance was studied before treatment and after 6 and 24 months of growth-promoting treatment with recombinant human growth hormone (24 IU/m<sup>2</sup>/week; 8 mg/m<sup>2</sup>/week) and oxandrolone (0.06 mg/kg/day), as well as after termination of the treatment. One girl developed an overt non-ketotic diabetes mellitus 50 months after termination of treatment. The results of the remaining 17 girls in whom the effect of treatment on glucose metabolism was reversible are presented as a group. Their median age at the beginning of the treatment was 10.4 years (range 6.9–15.9), and 15.0 years (range 12.1–19.9) at the final assessment. There was a moderate, but not significant rise in fasting glucose throughout the course of the longitudinal study. At oral glucose tolerance testing (oGTT), the area under the curve for glucose rose significantly (p = 0.013) during the period of treatment and returned to the basic value thereafter. Fasting insulin and especially the integrated insulin values (AUCi; area under the curve for insulin) during oGTT increased continuously during treatment, declined after termination of treatment but were still significantly (p = 0.04) higher than before treatment. Considering the fact that in untreated girls with Turner syndrome the fasting insulin and the AUCi increase with age, one can conclude that the insulinaemia returned to age-specific norm after termination of treatment. Thus the effect of a combined growth hormone and oxandrolone growth-promoting treatment on glucose metabolism was fully reversible in these 17 girls with Turner syndrome.
Hormonal Factors Influencing Weight and Growth Pattern in Craniopharyngioma
Authors: Pinto G. , Bussières L. , Recasens C. , Souberbielle J.C. , Zerah M. , Brauner R. 
Published: April 2003

Patients operated on for craniopharyngioma frequently suffer from hyperphagia and are obese, but their statural growth is normal despite growth hormone (GH) deficiency. We have evaluated the hormonal factors influencing changes in weight and growth in 17 children before and 1, 3–6, 12, and/or 24 months after surgical resection of a craniopharyngioma performed at 7.7 ± (SE) 1 years of age. Of these, 15 patients had a GH deficiency before surgery, and all had complete pituitary deficiency after it. The plasma fasting insulin concentrations before surgery were positively correlated with body mass index (BMI, kg/m<sup>2</sup>; p < 0.05), plasma insulin-like growth factors (IGFI, p = 0.03, and IGFII, p = 0.04), and leptin (p = 0.03). They increased significantly 1 month after surgery and continued to increase thereafter, whereas leptin increased significantly only 3–6 months after surgery, paralleling changes in BMI. The plasma fasting insulin concentrations before surgery were also positively correlated with the weight changes (12.3 ± 2.3 kg, p < 0.01) during the 12 months after surgery, but not with changes in BMI SDS (3.1 ± 0.5, p = 0.07). Both expressions of weight change were correlated with the concomitant growth rates (4.8 ± 0.7 cm, p < 0.01). IGFI was above the 10th percentile for children with idiopathic short stature in 10 of 15 patients with craniopharyngioma-induced GH deficiency and IGF-binding protein 3 in 14 of 15 patients. Craniopharyngioma itself modified the control of insulin secretion, and surgery increased the insulin secretion which continued in the same way in a given patient after surgery. The increased insulin secretion in turn increases weight and keeps IGFI nearly normal. This may explain the normal growth rate despite the complete lack of GH.
Antiproliferative Effect and Cell Cycle Modulation by Melatonin on GH<sub>3</sub> Cells
Authors: Fornas Oscar , Mato M. Eugenia , Webb Susan M. 
Published: April 2003

We have investigated the effect of melatonin on cell proliferation and modulation, in the GH<sub>3</sub> experimental rat pituitary cell line; the expression of oncogenes c-<i>myc</i>, c-<i>jun</i> and the tumor suppressor gene p53 were also analyzed basally and after exposure to melatonin (10<sup>–6</sup>, 10<sup>–8</sup> and 10<sup>–10</sup> <i>M</i>). Melatonin exhibited an antiproliferative effect at all the doses tested, decreasing the proliferating index by 50%. After exposure to melatonin, a decrease in Ki67 and Proliferation cell nuclear antigen occurred acute- and transiently (at 2 h) after a single dose which recovered at 4 h, as well as chronically after repeated 12-hour doses which persisted at 48 h; a similar behavior was observed both acute- and chronically for c-<i>myc</i> and c-<i>jun</i>, while it was opposite for p53, rising acute- and transiently as well as after repeated exposure. These results demonstrate that melatonin modulates the proliferation mechanisms of the GH<sub>3</sub> cells.
Sodium Salicylate-Induced Apoptosis of Human Peripheral Blood Eosinophils Is Independent of the Activation of c-Jun N-Terminal Kinase and p38 Mitogen-Activated Protein Kinase
Authors: Wong C.K. , Zhang J.P. , Lam C.W.K. , Ho C.Y. , Hjelm N.M. 
Published: April 2003

<i>Background:</i> It has been shown that the inhibition of eosinophilic apoptosis is an important mechanism for the development of blood and tissue eosinophilia in allergic diseases. Considerable attention has recently been focused on the role played by different intracellular kinase cascades in the control of apoptosis. In the present study, we investigated the effect of sodium salicylate (NaSal), a nonsteroidal anti-inflammatory drug, on mitogen-activated protein kinases (MAPK) and apoptosis of human eosinophils. <i>Methods:</i> Human blood eosinophils were purified from buffy coat. NaSal-induced apoptosis of eosinophils was assessed by morphological changes and Annexin-V binding assay. Changes of MAPK activity upon treatment with NaSal were measured by kinase activity assay and Western blot. <i>Results:</i> NaSal could induce apoptosis of human blood eosinophils in a dose- and time-dependent manner. It could also activate c-Jun N-terminal kinase (JNK) and p38 MAPK but not extracellular signal-regulated protein kinase (ERK) activity within 1 h. Pretreatment of eosinophils with p38 MAPK and JNK anti-sense (AS) phosphorothioate oligodeoxynucleotides (ODN) or specific p38 MAPK inhibitor SB 203580 did not have any significant effect on NaSal-induced apoptosis. However, ERK AS ODNs could trigger the apoptosis of normal eosinophils. <i>Conclusion:</i> There is no direct relationship between the activation of JNK and p38 MAPK pathways and NaSal-induced apoptosis in human peripheral blood eosinophils.
Increased Eosinophil Cation Protein Level in Sensitized Nonasthmatics Is Linked to Subsequent Hyperresponsiveness to Methacholine
Authors: Rasmussen F. , Lambrechtsen J. , Siersted H.C. , Hansen H.S. , Hansen N.C.G. 
Published: April 2003

<i>Background:</i> Increased levels of eosinophil cation protein (ECP) in sensitized subjects may reflect early stages of an ongoing inflammatory process and therefore precede asthma and bronchial hyperreactivity. <i>Aim:</i> To study whether nonasthmatic subjects with sensitization to allergens and increased ECP levels are at a higher risk for subsequent increased bronchial reactivity compared with sensitized nonasthmatics with normal ECP levels. <i>Methods:</i> A prospective study of 240 schoolchildren with a mean age of 13.9 years (range: 12.6–15.9) who were followed up after 6.3 years. Bronchial reactivity was assessed by methacholine provocation testing. Sensitization was defined by one or more positive reactions (>3 mm wheal) to 10 common aeroallergens by skin prick testing. Increased ECP was defined as values above 20 μg/l. This separated the subjects into four categories: group 1: healthy controls without sensitization (n = 147); group 2: sensitized subjects with a serum ECP below 20 μg/l (n = 55); group 3: sensitized subjects with an ECP level at or above 20 μg/l (n = 16), and group 4: all asthmatics (n = 22). <i>Results:</i> Bronchial reactivity was similar in subjects of groups 2 and 3 at baseline (p = 0.8). Six years later, subjects from group 3 were more responsive to methacholine compared with subjects from group 2 (median: 12.7 versus 20.5 μmol; p < 0.05). In a logistic regression with hyperresponsiveness to methacholine at follow-up as dependent variable, the odds ratios (OR) for the groups were, with group 1 as reference: group 2: OR = 2.2 (0.8–6.6: p = 0.2), group 3: 5.9 (1.6–21.7: p < 0.01). <i>Conclusion:</i> Subjects with sensitization and increased ECP levels are subsequently more airway-responsive to methacholine compared with sensitized subjects with normal ECP levels. This supports the hypothesis that sensitization is linked to increased bronchial reactivity through a process in which markers of inflammation are involved.
Purification and Immunobiochemical Characterization of Folding Variants of the Recombinant Major Wasp Allergen Ves v 5 (Antigen 5)
Authors: Suck Roland , Weber Bernhard , Kahlert Helga , Hagen Susan , Cromwell Oliver , Fiebig Helmut 
Published: April 2003

<i>Background:</i> Antigen 5 is one of three major allergens in wasp venoms, but unlike phospholipase A<sub>1</sub> and hyaluronidase, both of which are enzymes, its biological function is unknown. The cDNA coding for this allergen has been isolated and used for recombinant expression. Thorough analysis of the expression product is essential in order to evaluate the usefulness for in vivo or in vitro application. <i>Objective:</i> In this study, folding variants of the recombinant major allergen Ves v 5 from <i>Vespula vulgaris</i> were immunologically and biochemically investigated in order to determine their possible applicability for diagnostic or therapeutic purposes. <i>Method:</i> The cDNA encoding Ves v 5 was cloned into the expression vector pSE420 which generates recombinant products lacking a tag sequence. After expression, inclusion bodies were purified, subsequently denatured and dialyzed against different solutions. The structural properties of soluble proteins were analyzed by size exclusion chromatography, non-reducing SDS-PAGE, native PAGE, N-terminal sequencing, proteolytic digestion and ion exchange chromatography. Immunological investigations were performed by using different monoclonal antibodies (mAbs) specific for Ves v 5 and IgE from patients allergic to wasp venom allergens. <i>Results:</i> After dialysis, soluble monomeric recombinant Ves v 5 was more than 95% pure in each case. Using different dialysis solutions, clearly distinguishable folding variants were obtained. In one case, the recombinant allergen was comparable with the natural counterpart in respect of migration in non-reducing SDS-PAGE, native PAGE and IgE reactivity. This variant reacted with two different Ves v 5-specific mAbs and produced a stable fragment after proteolytic digestion. Elution from a cation exchange chromatography column was achieved with 320 m<i>M</i> NaCl. In two other cases, folding variants exhibited a different migration behavior in SDS-PAGE and native PAGE compared with the natural allergen. Also, the mAb 1E11 recognized none of these variants since it presumably detected a conformational epitope. Moreover, the IgE reactivity was clearly reduced and proteolytic digestion effected almost complete degradation. These variants eluted from the cation exchange column with 400 m<i>M</i> NaCl. <i>Conclusion:</i> Defined folding strategies resulted in both soluble misfolded variants with reduced IgE reactivity, potentially suitable for immunotherapy, and natural-like folded variants for diagnosis.
Inhibitory Effects of Human Neutrophil Functions by the 45-kD Glycoprotein Derived from the Parasitic Nematode <i>Trichinella spiralis</i>
Authors: Bruschi Fabrizio , Carulli Giovanni , Azzarà Antonio , Homan Wieger , Minnucci Sistina , Rizzuti-Gullaci Angela , Sbrana Silverio , Angiolini Claudia 
Published: April 2003

<i>Aim:</i> We evaluated the effect of the 45-kD protein of <i>Trichinella spiralis</i> (gp45), purified by affinity chromatography, on random migration and chemotaxis, the oxidative metabolism of human neutrophils and on the CD11b upregulation induced by formyl-methionyl-leucyl-phenylalanine (f-MLP). <i>Methods:</i> Donor neutrophils incubated with different amounts of gp45 (0.5, 1, 1.5, 2 μg/ml) or buffer and the random migration and chemotaxis, evaluated by means of a special technique of image analysis, and the chemiluminescence response to f-MLP or phorbol myristate acetate (PMA) were analyzed. The effect on CD11b upregulation was assessed incubating cells with the protein, when activating them with f-MLP. <i>Results:</i> The results showed that gp45 inhibited both random and stimulated migrations, and reduced the response to f-MLP and PMA. Furthermore, gp45 significantly reduced the upregulation of the CD11b induced by f-MLP. <i>Conclusion:</i> The results show that gp45 inhibits PMN in different functions, suggesting an anti-inflammatory action.
Effects of Perilla Seed Oil Supplementation on Leukotriene Generation by Leucocytes in Patients with Asthma Associated with Lipometabolism
Authors: Okamoto Makoto , Mitsunobu Fumihiro , Ashida Kozo , Mifune Takashi , Hosaki Yasuhiro , Tsugeno Hirofumi , Harada Seishi , Tanizaki Yoshiro , Kataoka Mikio , Niiya Kenji , Harada Mine 
Published: April 2003

<i>Background:</i> Dietary sources of α-linolenic acid, such as perilla seed oil, may have the capacity to inhibit the generation of leukotrienes (LTs) by leucocytes in patients with asthma, as has been reported with the consumption of other long-chain n-3 fatty acids. <i>Methods:</i> The factors affecting the suppression of leukotriene (LT) C4 generation by leucocytes were examined by comparing the clinical features of patients with asthma who had been given dietary perilla seed oil (n-3 fatty acids). Group A consisted of patients in whom the leucocyte generation of LTC4 was suppressed by dietary perilla seed oil. Group B consisted of those in whom LTC4 generation was not suppressed. <i>Results:</i> LTC4 generation by leucocytes decreased significantly in group A after 2 (p < 0.05) and 4 weeks (p < 0.05); conversely, it increased significantly in group B after 4 weeks (p < 0.05). The two study groups differed significantly in terms of LTC4 generation by leucocytes after 4 weeks of dietary supplementation (p < 0.05). Ventilatory parameters such as peak expiratory flow (PEF), forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV<sub>1</sub>) increased significantly after 4 weeks of dietary supplementation in group A (p < 0.05). Values of PEF, FVC, FEV<sub>1</sub> and maximum expiratory flow at 25% of the forced vital capacity (&#118;&#775;<sub>25</sub>) differed significantly between groups A and B prior to dietary supplementation. Serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol and phospholipid were significantly decreased by dietary supplementation in group A after 4 weeks. Serum levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, LDL cholesterol and phospholipid differed significantly between the two study groups prior to dietary supplementation. Serum levels of triglyceride and LDL cholesterol differed significantly between the two study groups after 4 weeks of dietary supplementation. <i>Conclusions:</i> Dietary supplementation with perilla seed oil in selected patients with asthma suppresses the generation of LTC4 and is associated with clinical features such as respiratory function and lipometabolism.
Transmission of IgA and IgG Monoclonal Antibodies to Mucosal Fluids following Intranasal or Parenteral Delivery
Authors: Falero-Diaz Gustavo , Challacombe Stephen , Rahman Durdana , Mistry Mukesh , Douce Gill , Dougan Gordon , Acosta Armando , Ivanyi Juraj 
Published: April 2003

<i>Background:</i> The efficacy by which passive antibodies can reach the lungs could be important for the outcome of immunotherapy of respiratory pulmonary infections. We examined how transmission to a number of mucosal sites is affected by the route of inoculation. <i>Methods:</i> Transmission of newly raised IgA class Mabs against mycobacterial surface antigens to saliva, lung or vaginal lavage, bile and serum of BALB/c mice was compared with existing IgG Mabs. ELISA was used for testing body fluids obtained 1–24 h after intranasal or intravenous inoculation and 1–7 days following back-pack tumour growth of hybridomas. <i>Results:</i> Intranasal inoculation resulted in a rapid rise and high levels of both IgA and IgG class Mabs in lung lavage. In contrast, following intravenous Mab injection or back-pack tumour growth of hybridoma cells, effective lung transmission was observed for the IgG1 and IgG2b MAbs, but not for the IgA Mabs. The secretory component was acquired by the transmitted IgA MAbs in the mucosal fluids, but not in the serum. Nevertheless, the time course of mucosal IgA antibody levels was similar to that of the tested IgG Mabs. Furthermore, the relative proportion of transmission to saliva and bile varied between individual Mabs indicating a role of tissue-specific, immunoglobulin class-unrelated mechanisms. <i>Conclusions:</i> Intranasal, rather than parenteral inoculation of mice is required for the efficient delivery of IgA antibodies against respiratory pulmonary pathogens. Interestingly, IgA-secretory component complexing of intranasally applied Mabs did not significantly influence their persistence in the lungs.
Involvement of Eosinophils in the Early-Phase Allergic Reaction in a Guinea Pig Rhinitis Model
Authors: Imai Norio , Miyahara Atsushi , Yamazaki Yuji , Homma Reiko , Ino Yoshitaka , Kurumi Masateru 
Published: April 2003

<i>Background:</i> Eosinophils are found in the nasal lavage fluid (NLF) and nasal biopsies of patients with allergic rhinitis after a nasal antigen challenge, and associated not only with a late-phase allergic reaction (LPR) but also an early phase allergic reaction (EPR). Numerous studies have been carried out to clarify the participation of eosinophils in LPR or airway hyperresponsiveness. However, there has been no published report describing in detail the role of eosinophils during EPR. To better understand the involvement of eosinophils in EPR, we studied the effects of repeated antigen challenges on nasal airway responsiveness and eosinophilic inflammation in EPR using a guinea pig rhinitis model. <i>Methods:</i> Nasal airway responsiveness was measured as the nasal airway resistance (NAR) after nasal antigen provocation. Eosinophilic inflammation during EPR was assessed by nasal lavage and histopathological examination using two groups of animals: those in group 1 were subjected to a sensitization pretreatment only, and those in group 2 were subjected to a pretreatment of sensitization followed by repeated nasal challenges. <i>Results:</i> Repeated antigen challenges induced nasal hyperresponsiveness as indicated by a decrease in the antigen provocation dose and a significant increase in NAR. Furthermore, significant increases in eosinophil counts, eosinophil peroxidase (EPO) activity and protein content in NLF during EPR were observed following antigen provocation in group 2. There were significant correlations between the levels of these parameters, and albumin was the most prevalent of the proteins in NLF. Histopathological examination showed that the degree of eosinophil infiltration into the lamina propria of the nasal mucosa of the animals in group 2 was significantly and apparently higher than in group 1. Particularly, epithelial disruption and mucosal edema were significantly elevated after antigen provocation in group 2. <i>Conclusions:</i> These results suggest that chronic eosinophil accumulation is induced by repeated antigen challenges in the nasal tissue, and that once antigen provocation occurs, eosinophils in the tissue are activated and responsible for the amplification of EPR such as vascular permeability and mucosal edema.
Monoclonal Antibodies against Der s 1, a Major Allergen of <i>Dermatophagoides siboney</i>
Authors: Sewer Minerva , Uyema Keiko , Labrada Mayrel , González Maritza , Coca Marcos 
Published: April 2003

Six stable clones secreting murine monoclonal antibodies (Mabs) against Der s 1 were obtained. The binding of Mabs showed cross-reactivity with <i>Dermatophagoides farinae</i>, as determined by enzyme-linked immunosorbent assay (ELISA). In a Western blot assay, antibodies reacted with a 24-kD protein considered to represent the major allergen Der s 1. The repertoire of antigenic sites on Der s 1 was studied using a panel of Mabs. Epitope specificity of the Mabs was determined by both competitive inhibition and sandwich ELISA assays. The results defined six different, non-overlapping and non-repeated antigenic sites on the allergen molecule. Der s 1 allergen from <i>Dermatophagoides siboney</i> extracts was purified by Mab affinity chromatography, this procedure gave 43% recovery of >90% pure allergen. The purified allergen had capacity to bind specific human IgE and demonstrated an allergenic activity of up to 77% of total <i>D. siboney</i> extract. An Mab-ELISA was developed using Mabs directed against different epitopes on Der s 1. This assay could detect up to 1 ng/ml of Der s 1 and Der f 1 in allergen preparations.
Invasion Strategies of the Oral Pathogen <i>Porphyromonas gingivalis:</i> Implications for Cardiovascular Disease
Authors: Deshpande Rajashri G. , Khan Mahfuz , Genco Caroline Attardo 
Published: April 2003

Microorganisms have evolved a variety of mechanisms designed to evade detection and/or destruction by the host. Many pathogens evade host defenses by invading cells, thus providing the bacterium with an environment free of competing microorganisms. Adherence and invasion are active processes in which microorganisms often use host proteins and enzymes to gain entry into the cell, thus stimulating their own uptake. The investigation of invasion by the periopathogen <i>Porphyromonas gingivalis</i> is in its infancy in comparison with that of the enteric pathogens. However, recent studies with <i>P. gingivalis</i> have revealed that these organisms have developed invasion strategies and mechanisms similar to those of the enteric pathogens for both epithelial and endothelial cells. The study and elucidation of the mechanisms by which microorganisms such as <i>P. gingivalis</i> persist in chronic infection will provide valuable insight into the pathogenesis of <i>P. gingivalis</i>-mediated periodontal disease. The ability to multiply in and to activate endothelial cells may be one of the pathogenic mechanisms exerted by <i>P. gingivalis</i> that may explain the recently described association between this organism and cardiovascular disease.