bluuebunny/crossref_metadata_2025 huggingface dataset:
Precore Wild-Type Hepatitis B Virus with G1896 in the Resolution of Persistent Hepatitis B Virus Infection
Authors: Kobayashi Mariko , Arase Yasuji , Ikeda Kenji , Tsubota Akihito , Suzuki Yoshiyuki , Saitoh Satoshi , Kobayashi Masahiro , Suzuki Fumitaka , Akuta Norio , Hosaka Tetsuya , Someya Takashi , Matsuda Marie , Sato Junko , Takagi Kimiko , Miyakawa Yuzo , Kumada Hiromitsu
Published: July 2003

Objective: Factors influencing the resolution of persistent hepatitis B virus (HBV) infection were sought for. Methods: The loss of hepatitis B surface antigen (HBsAg) from serum was correlated with mutations in HBV DNA for a hepatitis B e antigen (HBeAg)-minus phenotype in patients infected with HBV genotype C and positive for HBeAg at presentation. Results: HBeAg turned negative in all the 22 patients in whom HBV infection resolved, but only in 11 of the 25 patients with severe liver diseases (100 vs. 44%, p = 0.0001). The precore wild type (G1896) persisted significantly more frequently in the 22 patients in whom HBV infection resolved than in the 11 patients who developed decompensated liver cirrhosis or hepatocellular carcinoma (15/22 or 68% vs. 1/11 or 9%, p = 0.005). The double mutation in the core promoter (T1762/A1764) was comparably frequent in the two groups of patients at presentation (14/22 or 64% vs. 7/11 or 64%) and >15 years thereafter (18/22 or 82% vs. 10/11 or 91%). Conclusion: The precore wild type (G1896) would seem to facilitate the resolution of HBV infection, while the precore mutant (A1896) may induce severe liver diseases in patients with HBeAg-positive chronic hepatitis who have lost HBeAg from serum.
Histological Improvements after a Three-Year Lamivudine Therapy in Patients with Chronic Hepatitis B in Whom YMDD Mutants Did Not or Did Develop
Authors: Suzuki Yoshiyuki , Arase Yasuji , Ikeda Kenji , Saitoh Satoshi , Tsubota Akihito , Suzuki Fumitaka , Kobayashi Masahiro , Akuta Norio , Someya Takashi , Miyakawa Yuzo , Kumada Hiromitsu
Published: July 2003

Objective: The long-term effects of lamivudine and the influence of YMDD mutants on the histology of chronic hepatitis B are not known. Methods: 3-year lamivudine therapy was given to 16 patients with chronic hepatitis B. YMDD mutants did not develop in 9 patients (group A), while they appeared in the remaining 7 patients (group B). Results: Biochemical and virological responses were invariably achieved in the 9 patients without YMDD mutants, while virological breakthroughs with or without biochemical relapses occurred in all 7 patients with such mutants. All 16 patients accomplished histological improvement, with the total histology activity index (HAI) score decreasing from 11.3 ± 3.0 to 4.1 ± 1.7 (p < 0.001). The total HAI score decreased from 11.6 ± 3.8 to 3.4 ± 1.3 in the 9 patients in group A (p < 0.001). Although to a significantly lesser extent (p < 0.02), the total HAI score also decreased in the 7 patients in group B from 10.9 ± 1.0 to 5.0 ± 1.7 (p < 0.001). Conclusion: The results obtained indicate that 3-year lamivudine therapy can induce histological improvements, regardless of the appearance of YMDD mutants accompanied by virological breakthroughs and biochemical relapses.
Lack of Epidemiological Evidence for a Role of Resolved Hepatitis B Virus Infection in Hepatocarcinogenesis in Patients Infected with Hepatitis C Virus in Japan
Authors: Hiraoka Tetsuro , Katayama Keiko , Tanaka Junko , Ohno Naofumi , Joko Kouji , Komiya Yutaka , Kumagai Junko , Mizui Masaaki , Hino Kunihiko , Miyakawa Yuzo , Yoshizawa Hiroshi
Published: July 2003

Objective: The role of resolved hepatitis B virus (HBV) infection in promoting hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV) in Japan was evaluated by epidemiological surveys. Methods: Antibody to hepatitis B core (anti-HBc) was determined in age-matched blood donors, and the frequency was compared with that in patients with HCV-associated HCC in Japan. Results: Anti-HBc was detected significantly more frequently in the blood donors with than without antibody to HCV (anti-HCV; 76/135 or 56.3% vs. 65/255 or 25.5%, p < 0.001). In the patients with HCV-associated HCC, anti-HBc was detected in 109 of 202 (54.0%), which was comparable to the frequency in anti-HCV-positive blood donors (56.3%). Among the blood donors with anti-HCV, the prevalence of anti-HBc was no different between those with and without HCV RNA in serum (40/77 or 51.9% vs. 36/58 or 62.1%). Conclusions: The individuals of an age with high cancer frequency (≧40 years) in Japan would have been exposed to HBV frequently (>50%), whether or not they have developed HCV-associated HCC. Despite repeated assertions in the literature, no epidemiological evidence was obtained for a role of past HBV infection in hepatocarcinogenesis in patients infected with HCV in Japan.
Association of L Protein and in vitro Tomato Spotted Wilt Virus RNA-Dependent RNA Polymerase Activity
Authors: Chapman Elisabeth J. , Hilson Pierre , German Thomas L.
Published: July 2003

We have previously described an in vitro assay for RNA-dependent RNA polymerase activity in virions of tomato spotted wilt virus (TSWV). Here we report antibody inhibition of virion-associated RNA synthesis in vitro with an L-protein-specific polyclonal antibody raised against the carboxy-terminus of the L protein. In contrast, RNA synthesis was not inhibited by a heterologous antiserum and was unaffected by antiserum raised against an internal portion of the L protein. Our results directly associate the TSWV L protein, the putative viral polymerase, with RNA synthesis functions in vitro.
Efficacy of Lamivudine Therapy and Factors Associated with Emergence of Resistance in Chronic Hepatitis B Virus Infection in Japan
Authors: Suzuki Fumitaka , Tsubota Akihito , Arase Yasuji , Suzuki Yoshiyuki , Akuta Norio , Hosaka Tetsuya , Someya Takashi , Kobayashi Masahiro , Saitoh Satoshi , Ikeda Kenji , Kobayashi Mariko , Matsuda Marie , Satoh Junko , Takagi Kimiko , Kumada Hiromitsu
Published: July 2003

Objective:  Several reports have examined the efficacy of long-term lamivudine therapy and the risk factors involved in emergence of viral resistance in Japanese patients with hepatitis B virus (HBV) infection. However, the patient cohorts in such studies are relatively small. Methods: We analyzed 234 chronically HBV-infected Japanese patients who were treated with lamivudine for more than 12 months. They comprised patients with HBV genotype A (n = 8), genotype B (n = 21), genotype C (n = 203) and other HBV genotypes (n = 2). Results: In most patients, lamivudine resulted in normalization of alanine transaminase (ALT) levels at 6 and 12 months, and suppression of serum HBV DNA to undetectable levels by the branched chain DNA probe assay (bDNA). Rates of ALT normalization and non-detection of HBV DNA were higher among patients with genotype B than genotype C disease. The proportions of patients who achieved HBeAg loss were 27, 42 and 45% after 6 months, 1 year and 2 years, respectively. The emergence of mutations was not different among genotypes A, B and C by the Kaplan-Meier method. Multivariate analyses identified high HBV DNA level (bDNA ≧100 MEq/ml) as an independent factor associated with emergence of the YMDD motif mutation in all patients. Among patients with genotype C disease, which is the predominant HBV genotype in Japan, multivariate analysis also identified high HBV DNA level and HBeAg positivity as factors associated with emergence of resistance. Conclusion: Patients exhibiting these factors at the commencement of lamivudine treatment must be monitored carefully at regular intervals for emergence of viral resistance.
Establishment of Respiratory Syncytial Virus Persistence in Cell Lines: Association with Defective Interfering Particles
Authors: Valdovinos Mirza Romero , Gómez Beatríz
Published: July 2003

Defective interfering particles (DIP) have frequently been advanced to explain the persistence of virus in vitro. However, DIP involvement in the establishment of respiratory syncytial virus (RSV) persistence in cell lines has not been documented. We report establishment of RSV persistence in human epithelial larynx (HEp-2) and lung (H358) cell lines by infection with RSV enriched with DIP. Viral persistence in HEp-2 and H358 has been stably maintained for >3 years without apparent cytopathic effect or periodic crises. Persistent cultures resisted superinfection with the original virus and no cyclic variations in infectious virus and DIP yields were observed. During passages, low levels of infectious RSV and defined species of DIP were produced. Moreover, 80–90% of the cells exhibited viral antigen. Persistence in H358 cells was established with a buoyant density band containing DIP and infectious virus obtained from a H358 persistently infected culture. Thus, DIP are required for establishment of RSV persistence cultures in human epithelial cell lines; however, DIP per se are not able to establish persistence.
Ubiquitous Embryonic Expression of the Norepinephrine Transporter
Authors: Ren Z.G. , Pörzgen P.P. , Youn Y.-H. , Sieber-Blum M.
Published: July 2003

We report that the norepinephrine transporter (NET) is expressed in avian and mouse embryos by numerous tissues that are derived from all three germ layers. In the nervous system, NET is expressed in the neuroepithelium of the brain and the spinal cord (ventral horn and floor plate), forming mesencephalic nuclei, neural crest, dorsal root ganglion, sympathetic ganglion and spinal nerve. Nonneuronal embryonic NET-expressing structures include the olfactory epithelium, the notochord, the somitic dermamyotome and mesenchymal cells in the limb bud. NET is expressed prominently in the cardiovascular system, including endothelial cells of forming blood vessels, the walls of the aorta and veins, the epicardium, myocardium and a subset of blood cells. The gut, lung buds, and in particular the kidneys, are intensely NET immunoreactive. Since neurotransmitters are known to affect proliferation, survival and differentiation of many mesenchymal cell types, NET function may be a physiologically relevant regulatory element in embryonic development. A working model is proposed for neurotransmitter transporter function in the embryo as a system for the concentration and targeted delivery of neurotransmitter.
Developmental Neurotoxicity of Toluene: in vivo and in vitro Effects on Astroglial Cells
Authors: Burry Mark , Guizzetti Marina , Oberdoerster Jan , Costa Lucio G.
Published: July 2003

Toluene, an inexpensive and available industrial solvent, has become increasingly popular as a drug of abuse. Inhaling toluene leads to a feeling of euphoria and several reports have shown that children born to women who had abused toluene during pregnancy present a syndrome (toluene embryopathy or fetal solvent syndrome) that is characterized by CNS effects (e.g. microencephaly), growth retardation and facial dysmorphologies. The characteristics of the fetal solvent syndrome are very similar to those observed in the fetal alcohol syndrome. As exposure of rats to ethanol during the brain growth spurt has been shown to cause microencephaly and to affect glial cell proliferation and maturation, the present study examines the effects of toluene administration (250, 500 and 750 mg/kg) in neonatal rats from postnatal day 4 to 10. This treatment resulted in a significant decrease in both brain and body weights, and in a significant reduction of levels of glial fibrillary acidic protein, but not of neuron-specific enolase in rat brain. In vitro experiments demonstrate that pharmacologically relevant concentrations of toluene (250–1,000 µM) significantly inhibit proliferation of rat cortical astrocytes without causing overt cytotoxicity. These results indicate that toluene does not cause selective microencephaly; however, it affects brain weight, and appears to target developing astrocytes, possibly by inhibiting their proliferation.
Self-Biting Induced by Activation of L-Type Calcium Channels in Mice: Dopaminergic Influences
Authors: Kasim Suhail , Jinnah H.A.
Published: July 2003

The L-type calcium channel activator ±Bay K 8644 induces repetitive self-biting and self-injurious behavior in young mice. Since dopaminergic systems have been implicated in prior studies of these behaviors in both humans and animals, the present experiments were designed to test whether drugs influencing the dopaminergic systems could modify the behavioral responses to ±Bay K 8644. The ability of ±Bay K 8644 to provoke self-biting and self-injurious behavior was increased by amphetamine and GBR 12909, drugs that augment synaptic dopaminergic concentrations by blocking the reuptake and/or stimulating the release of dopamine. Conversely, self-biting and self-injurious behavior were decreased by tetrabenazine or reserpine, two drugs that deplete vesicular stores of dopamine. These results suggest that dopaminergic systems may play a role in the ability of ±Bay K 8644 to provoke self-biting and self-injurious behavior.
Postnatal Touch Stimulation Acutely Alters Corticosterone Levels and Glucocorticoid Receptor Gene Expression in the Neonatal Rat
Authors: Jutapakdeegul N. , Casalotti Stefano O. , Govitrapong P. , Kotchabhakdi N.
Published: July 2003

Environmental manipulation early in life can alter the development of the hypothalamic-pituitary-adrenal (HPA) axis by mechanisms that are still unclear. The aim of the present work was to study the acute effects of postnatal touch stimulation, in an attempt to understand the mechanism by which touch stimulation early in life alters the HPA response to stress in adult animals. Rat pups were gently brushed for 15 min daily during the 1st postnatal week. Serum corticosterone levels were determined by radioimmunoassays, while glucocorticoid receptor (GR) gene expression was assayed by semiquantitative reverse transcriptase-polymerase chain reaction. Touch stimulation induced a significant decrease (30–36%) in serum corticosteroid secretion during the 1st and 2nd postnatal day as compared to the unstimulated group. In contrast, GR gene expression in the touch stimulation group was significantly increased in several brain areas such as the hippocampus (19–21%), frontal cortex (26–34%) and midbrain (15–24%). The results thus indicate that neonatal touch stimulation causes acute hormone- secretion and gene-expression changes within the period of stimulation. These changes may be the underlying cause for the permanent changes that have been observed in adult animals touch-stimulated as neonates.
Treatment of Hypoxic-Ischemic Brain Injury in Newborn Rats with TPCK 3 h after Hypoxia Decreases Caspase-9 Activation and Improves Neuropathologic Outcome
Authors: Feng Yangzheng , LeBlanc Michael H.
Published: July 2003

N-Tosyl-L-phenylalanyl-chloromethyl ketone (TPCK) reduces apoptosis in vitro. Pretreatment with TPCK reduces brain injury. Would treatment after injury reduce damage? Seven-day-old rats had the right carotid artery ligated and were subjected to 2.5 h of 8% oxygen and were treated intraperitoneally 3 h after hypoxia with 10 mg/kg of TPCK or vehicle. Brain damage was measured 22 days after injury. bcl-2, bax, and cytochrome c where measured by Western blot 24 h after injury. Caspase-9 and caspase-3 activity were measured enzymatically 24 h after injury. Treatment with TPCK reduced the loss of the right hemisphere caused by injury from 27.6 ± 2.8% SEM (vehicle, n = 56) to 19.8 ± 2.8% (TPCK, n = 61, p < 0.05). Hypoxic ischemia increased cytosolic cytochrome c from 0.25 ± 0.04 to 0.4 ± 0.04 optical density (OD; p < 0.05), but TPCK had no effect (0.31 ± 0.03 OD). TPCK reduced caspase-9 activity from 72 ± 30 to 43 ± 5 fluorescence units/h/mg (p < 0.05 vs. vehicle), and caspase-3 activity from 66 ± 10 to 39 ± 3.7 fluorescence units/h/mg (p < 0.05 vs. vehicle). Treatment with TPCK 3 h after hypoxic ischemia reduced brain infarct size. TPCK may act by reducing caspase-9 activation by cytochrome c.
Maternal Hypothalamic-Pituitary-Adrenal Disregulation during the Third Trimester Influences Human Fetal Responses
Authors: Sandman Curt A. , Glynn Laura , Wadhwa Pathik D. , Chicz-DeMet Aleksandra , Porto Manuel , Garite Tom
Published: July 2003

Maternal peptides from the hypothalamic-pituitary-adrenal (HPA) axis rise during human pregnancy. The effects of circulating maternal adrenocorticotropin (ACTH) and β-endorphin (BE) on human fetal behavior was determined in 135 women during their 32nd week of gestation. Fetal behavior was measured by assessing heart rate habituation to a series of repeated vibroacoustic stimuli. Individual differences in habituation were determined by computing the number of consecutive responses above the standard deviation during a control period. There was no significant relation between levels of ACTH, BE and the rate of fetal heart rate habituation. However, an index of HPA disregulation (uncoupling of ACTH and BE) was related significantly to fetal behavior. Fetal exposure to high levels of maternal BE relative to ACTH was associated with significantly lower rates of habituation. Results indicate that maternal stress and stress-related peptides influence fetal response patterns. It is possible that this influence persists over the life span.
Notch1 and Numb Genes Are Inversely Expressed as Oligodendrocytes Differentiate
Authors: Givogri Maria I. , Schonmann Vilma , Cole Ruth , de Vellis Jean , Bongarzone Ernesto R.
Published: July 2003

The Notch1 pathway plays a fundamental role during the establishment of cell fates in the central nervous system (CNS) by regulating neural cell differentiation. In oligodendrocytes (OLs), Notch1 activity prevents these cells from becoming terminally mature, thereby influencing CNS myelination. Little is known of how OLs regulate the expression of this receptor at the gene level or if OLs have mechanisms to control the level of intracellular activity of the Notch1 pathway. In this study, we have found that Notch1 gene expression was higher in proliferative OL progenitor cells (OPCs) and was reduced when cells were forced to withdraw from the cell cycle and became mature, indicating that Notch1 gene expression is developmentally regulated in OLs. We observed that the blockade of terminal differentiation of OPCs by incubation with Delta1, an activator of Notch1, was a dominant process and OL-differentiating signals such as thyroid hormone could not overcome this inhibition in culture. This suggests that a downregulation of the Notch1 pathway might be required to allow OPCs to enter terminal differentiation. We also provide evidence that OPCs and OLs express the Numb gene, a known negative regulator of Notch1 activity. In vivo, Numb was found in postnatal OLs from cerebellar and cerebral white matter. In vitro, Numb expression showed to be inversely correlated to that of Notch1, with higher levels of Numb proteins in mature OLs, in association with myelin-like membranes.
Expression and Role of Low-Affinity Nerve Growth Factor Receptor (p75) in Spinal Motor Neurons of Aged Rats following Axonal Injury
Authors: Xie Yuanyun , Yao Zhibin , Chai Hong , Wong Wai-Man , Wu Wutian
Published: July 2003

Expression of low-affinity nerve growth factor receptor (p75) and its regulation in spinal motor neurons of aged rats following axonal injury were investigated by immunocytochemical staining with antibody against p75. Under normal conditions, approximately 60% of spinal motor neurons expressed p75 in aged rats whereas no p75 expression was observed in spinal motor neurons of young adult rats. We examined the effects of spinal motor neuron injury on aged rats by two approaches, i.e. distal axotomy and spinal nerve root avulsion. A 20% increase in the number of p75-positive motor neurons was observed in aged rats 2 weeks after distal axotomy after which it returned to normal by 8 weeks post-injury and remained constant. Following root avulsion, a transient and slight up-regulation of p75 expression was observed in injured motor neurons. The number of p75-positive motor neurons decreased quickly to below normal levels 1 week after lesion and progressively declined with time post-injury, 40% by 2 weeks, 33% by 4 weeks, 23% by 8 weeks, and 5.8% by 12 weeks compared with the normal controls. This study demonstrates that p75 is re-expressed in aged spinal motor neurons. Following axonal injury in aged rats, up-regulation of p75 seems to coincide with the survival of injured motor neurons. Potential roles of re-expression of p75 in aged motor neurons are discussed.
Inflammatory Response Associated with Axonal Injury to Spinal Motoneurons in Newborn Rats
Authors: Yuan Qiuju , Xie Yuanyun , So Kwok-Fai , Wu Wutian
Published: July 2003

Axonal injury in peripheral nerve results in massive motoneuron loss during development. The purpose of this study was to examine the response of phagocytic populations (brain macrophages, BMOs, versus microglia) after different types of axonal lesions (distal axotomy or avulsion) in newborn rats. The morphology, spatial location and activation state of these inflammatory cells were observed. Following spinal root avulsion, BMOs were signaled rapidly and specifically to the location of dying motoneurons in the spinal cord. A large number of BMOs were observed around the avulsed motoneurons on the lesioned side of the spinal cord 1 day following the lesion. These BMOs were large, round, and intensely stained by both antibodies against ED1 and OX-42. The number of BMOs decreased by 3 days and disappeared by 5 days after injury. At the same time, reactive microglia appeared in the lesioned area and rapidly reached the peak level by the 5th day following avulsion. These reactive microglia were medium in size with retracted cellular processes and were also intensely stained by both ED1 and OX-42 antibodies. The number and staining intensity of reactive microglia declined sharply by day 7 after the lesion. In contrast, after distal axotomy only microglia but not BMOs were observed in the lesioned area. These microglial cells were small in size with long and fine-branched processes. They were ED1-negative but OX-42-positive.
Secretory Phospholipases A2 as Multivalent Mediators of Inflammatory and Allergic Disorders
Authors: Granata Francescopaolo , Balestrieri Barbara , Petraroli Angelica , Giannattasio Giorgio , Marone Gianni , Triggiani Massimo
Published: July 2003

Phospholipases A2 (PLA2s) are enzymes responsible for mobilization of fatty acids, including arachidonic acid (AA), from phospholipids. These enzymes are classified as high-molecular-weight cytosolic PLA2s (cPLA2s) and low-molecular-weight secretory PLA2s (sPLA2s). There is increasing evidence that large quantities of sPLA2s are released in the plasma of patients with systemic inflammatory and autoimmune diseases. In addition, high levels of sPLA2s can be detected at sites of allergic inflammation including the upper airways of patients with rhinitis and the lower airways of patients with asthma. These extracellular enzymes play an important role in inflammation by releasing AA, which can be subsequently converted to proinflammatory prostaglandins and leukotrienes. Generation of AA mediated by sPLA2s occurs through different mechanisms, including (1) the direct hydrolysis of outer cell membrane phospholipids, (2) internalization and transfer of sPLA2s to intracellular pools of phospholipids enriched in AA, and (3) activation of cPLA2s. In addition, sPLA2s induce degranulation and production of cytokines and chemokines from a variety of cells involved in inflammatory and immune responses. These effects are exerted by mechanisms that are independent of the enzymatic activity and are mediated by the interaction of sPLA2s with specific or promiscuous membrane receptors. Therefore, sPLA2s may have an important role in inflammatory and allergic reactions by activating multiple mechanisms within inflammatory and immune cells, leading to the production of eicosanoids, cytokines and chemokines.
Pollen from Different Olive Tree Cultivars Contains Varying Amounts of the Major Allergen Ole e 1
Authors: Castro Antonio Jesús , de Dios Alché Juan , Cuevas Julián , Romero Pedro José , Alché Víctor , Rodríguez-García María Isabel
Published: July 2003

Background: Commercial olive pollen from uncertain cultivar origin is the common material used for clinical and biological studies. We aimed to assess the putative heterogeneity of olive cultivars with regard to the presence of the major pollen allergen Ole e 1 and to determine whether these differences have clinical relevance. Methods: The Ole e 1 content of several cultivars was determined by immunoblotting and ultrastructural immunocytochemistry and compared to that of a commercially available olive pollen extract designed for diagnosis. Reverse transcription-polymerase chain reaction analysis of Ole e 1 transcripts was also performed. Crude protein extracts were used to carry out skin prick tests (SPTs) on 30 allergic patients in order to evaluate the clinical importance of such differences. Results: Ole e 1 was present in all cultivars, although significant quantitative differences were detected. Ole e 1 transcripts positively correlated with the amount of the allergen. Significant variations in the average reactivity of allergic patients to SPTs were observed depending on the cultivar considered. Conclusions: The presence of the Ole e 1 allergen in all the cultivars suggests that this allergen may play an essential biological role. The expression of the allergen is controlled at the transcriptional level. The significant differences in the Ole e 1 content are likely responsible for the different average reactivity exhibited by patients to the cultivars studied, although the role of other allergens cannot be excluded. Our results suggest that the use of the commercial pollen mixtures currently available may lead to mistakes in allergy diagnosis and to limited success in immunotherapy. Therefore, further standardization is strongly recommended.
Specific Allergens Enhance Elastase Release in Stimulated Neutrophils from Asthmatic Patients
Authors: Monteseirín Javier , Bonilla Inés , Camacho M. Jesús , Chacón Pedro , Vega Antonio , Chaparro Antonio , Conde José , Sobrino Francisco
Published: July 2003

Background: The presence of the three forms of IgE receptor – the heterotrimeric high-affinity receptor for IgE (FcΕRI), the low-affinity receptor for IgE (FcΕRII/CD23) and the Mac-2/IgE-binding protein (ΕBP) – has been demonstrated on human neutrophils. We have previously shown that specific allergens are able to activate functional responses by neutrophils from allergic patients sensitized to those allergens. Neutrophils are present at the sites of allergic inflammation. The primary (azurophilic) granules of neutrophils contain a variety of enzymes, such as elastase, that might potentiate inflammation. It is not known whether specific allergens are able to elicit elastase release by neutrophils from allergic patients. In addition, we attempted to evaluate the relationship between neutrophil degranulation and lung function of the patients, measured as FEV1. Methods: Neutrophils were challenged in vitro with the specific allergens that produced clinical symptoms in asthmatic patients. The cells were also challenged with allergen to which the patients were not sensitive. Neutrophils from normal subjects were challenged with allergens as control. Results: The in vitro challenge of neutrophils with allergens to which the patients were sensitive elicited a release of elastase by these cells. The in vitro activation of neutrophils was highly allergen specific; allergens other than those accounting for clinical symptoms did not evoke elastase release, and allergens were ineffective on neutrophils from healthy donors. A significant inverse correlation was observed between elastase release and patients’ lung function, measured as FEV1. Conclusion: An IgE-dependent mechanism might promote elastase release by neutrophils at allergic sites. There is a significant inverse relationship between levels of elastase released by neutrophils from allergic patients and lung function, as assessed by FEV1.
Skin Tests and Conjunctival and Bronchial Challenges with Extracts of Blomia tropicalis and Dermatophagoides pteronyssinus in Patients with Allergic Asthma and/or Rhinoconjunctivitis
Authors: García Robaina J.C. , Sánchez Machín I. , Fernández-Caldas E. , Iraola Calvo V. , Vázquez Moncholi C. , Bonnet Moreno C. , de la Torre Morín F.
Published: July 2003

Background:Blomia tropicalis and Dermatophagoides pteronyssinus are important mite species in Tenerife, Canary Islands, Spain. Several studies have demonstrated a variable degree of allergenic cross-reactivity in vitro. However, only a few have addressed their allergenic cross-reactivity using challenge tests. Objective: The objective of this study was to conduct conjunctival and bronchial challenge tests with B. tropicalis and D. pteronyssinus extracts in a group of 42 patients with allergic asthma and/or rhinoconjunctivitis sensitised to house dust mites (31 females, 11 males; mean age 21.7 ± 7.02 years). Methods: Prick tests using standardised extracts and specific IgE determinations using the CAP system were performed. Bronchial and/or conjunctival challenges were conducted using freeze-dried extracts of both mite species. A patient was considered sensitive to a mite species if she/he had a positive prick and/or CAP test result. A total of 32 conjunctival and 15 bronchial challenges were performed with both mite species. Results: Prick tests were positive to B. tropicalis in 23 patients (54.7%) and to D. pteronyssinus in 41 (97.6%). One patient (2.4%) was exclusively sensitive to B. tropicalis. The CAP test was positive for B. tropicalis in 28 patients and for D. pteronyssinus in 41. Conjunctival challenges to B. tropicalis were positive in 20 patients (18 sensitised and 2 non-sensitised) and negative in 12 (5 sensitised and 7 non-sensitised patients). Conjunctival challenges with D. pteronyssinus were positive in all 31 D. pteronyssinus-sensitised patients who underwent conjunctival challenges. Bronchial challenges with B. tropicalis were positive in 9 sensitised patients and negative in 6 patients (2 sensitised and 4 non-sensitised). Bronchial challenges with D. pteronyssinus were positive in all patients except 1, who only reacted to B. tropicalis. Conclusions: Allergens of the mite species B. tropicalis induce positive conjunctival and bronchial challenges in B. tropicalis-sensitised individuals. Our results suggest that although there is a low to moderate degree of in vivo cross-reactivity between B. tropicalis and D. pteronyssinus, B. tropicalis seems to be a relevant source of allergens in areas where patients are exposed.
Theophylline Suppresses IL-5 and IL-13 Production, and Lymphocyte Proliferation upon Stimulation with House Dust Mite in Asthmatic Children
Authors: Kimura Mitsuaki , Okafuji Ikuo , Yoshida Takami
Published: July 2003

Background: Although theophylline has long been used as a medication for bronchial asthma (BA), much remains to be elucidated about its action on Th2 cells, which play a critical role in the development of BA. Objective: This study aimed to clarify the effect of theophylline on Th2 cells in an allergen-specific manner in children with BA. Methods: Peripheral blood mononuclear cells (PBMCs) from 32 children with BA were stimulated with house dust mite (HDM) or a purified HDM allergen Der f 1 in the presence or absence of theophylline at a therapeutic concentration (5–20 µg/ml). The proliferation of lymphocytes and the secretion of IL-5 and IL-13 were measured to estimate the influence of theophylline. Results: Theophylline at a concentration of 20 µg/ml significantly suppressed lymphocyte proliferation induced by 6-day culture with HDM or Der f 1. It also significantly reduced the production of IL-5 and IL-13 upon stimulation with HDM or Der f 1. Suppression of cytokine production and lymphocyte proliferation increased with concentrations of theopylline between 5 and 20 µg/ml. Conclusion: Theophylline suppresses the proliferation of lymphocytes and the production of proinflammatory Th2 cytokines, IL-5 and IL-13 induced by stimulation of PBMCs with HDM in children with BA.
Sera from Patients with Multiple Drug Allergy Syndrome Contain Circulating Histamine-Releasing Factors
Authors: Asero Riccardo , Tedeschi Alberto , Lorini Maurizio , Caldironi Gianni , Barocci Fiorella
Published: July 2003

Background: A subset of drug-intolerant patients show a marked propensity to react to several chemically unrelated antibacterial drugs. This condition is termed multiple drug allergy syndrome (MDAS). The pathogenesis of MDAS is still unclear. A possible mechanism is that a nonspecific patient-related factor leading to direct histamine release from mast cells and basophils is involved. We investigated whether a patient-related facilitating factor such as the clinically unapparent presence of circulating histamine-releasing factors may represent a nonspecific mechanism underlying drug-induced histamine release in patients with MDAS. Methods: 38 otherwise healthy adults with a history of acute urticaria following the ingestion of antibacterial drugs [18 subjects with MDAS (patients) and 20 monosensitive subjects (drug-allergic controls) on the basis of both clinical history and single-blind peroral challenges with alternative substances] and 20 subjects without a history of drug allergy (normal controls) underwent an autologous serum skin test (ASST). IgE specific for β-lactams was measured in sera from 25 subjects (11 patients and 14 drug-allergic controls) with a history of amoxicillin intolerance. Sera from 13 patients and 5 drug-allergic controls (all positive on ASST) were used in the in vitro histamine release assay using basophils from 3 normal donors. Results: 17 of 18 patients (94%) versus 8 of 20 drug-allergic controls (40%) showed an unequivocal wheal-and-flare reaction on ASST (p < 0.05). Skin reactions were generally more intense in the patient group. In one MDAS patient, the ASST was not assessable due to dermographism. No normal control was positive on ASST. Sera from 3 of 13 patients (23%) versus 0 of 6 drug-allergic controls (not significant) induced significant histamine release from basophils of normal donors. IgE specific for β-lactams was detected in sera from 1 of 11 patients (9%) versus 5 of 14 drug-allergic controls (36%) (not significant). Conclusion: Most patients with MDAS and more than one third of subjects with a history of hypersensitivity to a single antibacterial drug were characterized by the presence of circulating histamine-releasing factors. Such factors might play a role in drug-induced adverse reactions observed in these patients.
Reduction of IL-12 p40 Production in Activated Monocytes after Exposure to Diesel Exhaust Particles
Authors: Nilsen A.M. , Hagemann R. , Eikås H. , Egeberg K. , Nørkov T. , Sundan A.
Published: July 2003

Background: A reduction of IL-12 production by lung macrophages may partly explain the presumed adjuvant effect of diesel exhaust particles (DEP) in allergy and asthma. IL-12 stimulates T helper type 1 (Th1) lymphocytes, which inhibit Th2 cells via Th1-specific cytokines. The aim of this study was to investigate the influence of DEP on the production of IL-12 p40 in lipopolysaccharide (LPS)-activated monocytes. Methods: The human monocytic cell line Mono-Mac-6 was stimulated with LPS (200 ng/ml) and grown with DEP (0–200 µg/ml) for 0, 6 or 24 h. IL-12 p40 and the pro-inflammatory cytokine TNF were analysed in the cell supernatants by ELISA and a cell assay, respectively. Results: Levels of IL-12 p40 correlated inversely with the DEP exposure concentrations, whereas TNF increased in parallel to the DEP concentrations. At a DEP concentration of 200 µg/ml, the amount of IL-12 p40 was 35% of that observed without DEP. The corresponding TNF value was 230% of the control. Reduced viability, binding of cytokines to DEP or endotoxin in the DEP samples cannot fully explain the changes in the concentrations of these two cytokines. Conclusion: DEP seem to inhibit the production of IL-12 p40 and stimulate that of TNF in activated monocytes. This may partly explain the presumed adjuvant effect of DEP in atopy; by altering the Th1/Th2 balance via down-regulation of IL-12, the Th2 response characteristic of allergy and asthma may be favoured.
Oral Administration of Probiotic Escherichia coli after Birth Reduces Frequency of Allergies and Repeated Infections Later in Life (after 10 and 20 Years)
Authors: Lodinová-Zádníková Rája , Cukrowska Bożena , Tlaskalova-Hogenova Helena
Published: July 2003

Background: The development of allergies is a complex in which both composition and influence of the intestinal flora play an important role. We observed in earlier studies that the presence of an orally administered probiotic Escherichia coli strain in the intestine stimulated both a serum and local antibody response, decreased the presence of pathogens, the number of infections and the need for antibiotics. Methods: The preventive effect of oral colonization after birth with a probiotic E. coli strain was assessed by evaluating the results of a questionnaire both 20 years (150 full-term infants) and 10 years (77 preterm infants) after colonization. Results: Differences in occurrence of allergies in colonized and control subjects were statistically significant both after 10 and 20 years (p < 0.01). Specific serum IgE antibodies confirmed the presence of allergies in 100% of 10-year-old and 91% of 20-year-old patients with clinical symptoms of allergy. Ten years after colonization, the occurrence of repeated infections was significantly lower in colonized subjects than it was in controls (p < 0.01); 20 years later, no differences were found in these groups. Conclusions: Intentional colonization of the intestine with E. coli after birth (offering the advantage of the first colonizer) was found to decrease the incidence of allergies and repeated infections in later life.
Adoptive Transfer of Mast Cells Abolishes the Inflammatory Refractoriness to Allergen in Diabetic Rats
Authors: de Oliveira Barreto Emiliano , de Frias Carvalho Vinicius , Diaz Bruno Lourenço , Balduino Alex , Cordeiro Renato Sérgio Balão , Martins Marco Aurélio , Rodrigues e Sílva Patrícia Machado
Published: July 2003

Mast cells are pivotal secretory cells primarily implicated in allergen-evoked inflammatory responses and are downregulated following experimental chemical diabetes. Here we tested the hypothesis that a decrease in the number and reactivity of mast cells would account for the hyporesponsiveness of diabetic rats to allergen-induced inflammation. We found that the anaphylactic release of histamine from sensitized ileum, trachea and skin tissues was clearly reduced in rats turned diabetic via intravenous administration of alloxan. Likewise, actively and passively sensitized diabetic rats mounted a weaker allergen-evoked pleural mast cell degranulation and protein extravasation, as compared to sensitized nondiabetic animals, which paralleled a marked reduction in the mast cell population in the pleural cavity. The number of mast cells enumerated in the mesentery from diabetic rats was also clearly reduced. The allergen-evoked plasma leakage in diabetic rats was restored by the transfer of mast cells from sensitized nondiabetic rats. Moreover, the adoptive transfer of sensitized mast cells from diabetics to naive animals led to a lower allergen-induced exudation as compared to the response noted after the transfer of sensitized naive mast cells. Purified mast cells from diabetic rats were hyporesponsive to antigen and compound 48/80 stimulation in vitro as attested by histamine release. Thus, our results show that the phenomenon of refractoriness of diabetic animals to allergen challenge appears to be accounted for by a reduction in the number and reactivity of mast cells.
Max Sänger – Father of the Modern Caesarean Section
Authors: Hem Erlend , Børdahl Per E.
Published: July 2003

The major turning point in the development of the caesarean section appeared in 1882, when the German gynaecologist Max Sänger (1853–1903) suggested closing the uterine wound. Until this point, the wound was not sutured and so haemorrhage was a common cause of maternal death. Sänger’s method quickly became standard, leading to a spectacular drop in maternal mortality. Sänger was one of the most renowned German gynaecologists at the end of the 19th century. He contributed to the entire fields of obstetrics and gynaecology, in particular in founding Monatsschrift für Geburtshülfe und Gynaekologie, the predecessor of this journal.
Positron Emission Tomography with FDG in the Detection of Peritoneal and Retroperitoneal Metastases of Ovarian Cancer
Authors: Drieskens O. , Stroobants S. , Gysen M. , Vandenbosch G. , Mortelmans L. , Vergote I.
Published: July 2003

Objective: The aim of this prospective study was to evaluate 18F-FDG-PET, in comparison with CT, for the detection of peritoneal and retroperitoneal metastases of ovarian cancer. Methodology: 13 patients with primary (n = 7) or recurrent (n = 6) ovarian cancer underwent an attenuation-corrected 18F-FDG-PET of the abdomen as well as a contrast-enhanced abdominal CT, followed by surgical staging. For data analysis, the abdomen was artificially divided into six regions (right and left subphrenic region, right and left paracolic gutter, retroperitoneum and central abdomen). All images were reviewed and each region was visually scored on 18F-FDG-PET as well as on CT. 18F-FDG-PET results were compared with those of CT, using the surgical data as gold standard. Results: 73 regions were evaluable surgically and or histologically. Sensitivity was slightly better for CT than for 18F-FDG-PET (74 vs. 66%). Metastases of <5 mm were missed with both techniques. Specificity, however, was clearly better for 18F-FDG-PET than for CT (94 vs. 77%), especially in patients with recurrent disease, where postoperative changes (hematomas, adhesions, etc.) caused more false positive results on CT. Retroperitoneal lymph node involvement was found in 3/13 patients. The result of 18F-FDG-PET for the retroperitoneal lymph nodes was correct in all cases, whereas CT was false positive in 2 patients. 18F-FDG-PET is relatively inaccurate for the right and the left subphrenic region (missing tumor involvement in 5 patients compared to 2 patients for CT). Conclusion: Given the low sensitivity of both 18F-FDG-PET and CT for the detection of peritoneal metastases, surgical staging remains the gold standard. Because of the better specificity, 18F-FDG-PET might be preferred for evaluating residual or recurrent disease after surgery. 18F-FDG-PET was more sensitive in the retroperitoneal region than intraperitoneal.
Effect of Soy Supplementation on Endogenous Hormones in Postmenopausal Women
Authors: Foth Dolores , Nawroth F.
Published: July 2003

Aim: The purpose of this study was to investigate the effect of soy supplementation with isoflavones on plasma hormone levels in postmenopausal women. Methods: 16 postmenopausal women (mean age 56.21 ± 5.01 years) were assigned to 24 weeks of dietary soy supplementation. A defined soy protein amount per day (20 g) with a low dosage of isoflavones (20 mg) was used. Plasma samples were analyzed for estradiol, FSH, LH, prolactin, testosterone and DHEAS. Results: After 24 weeks of soy supplementation, plasma levels of estradiol did not increase. Gonadotropins, prolactin and the measured plasma androgens remained unchanged. We did not see any significant treatment effects. Conclusions: In the postmenopausal hypoestrogenic situation, soy protein consumption with low isoflavones does not influence endogenous hormone levels of estradiol and gonadotropins.
The Short-Term Effects of Different Regimens of Hormone Replacement Therapy on Left Ventricular Structure and Performance in Healthy Postmenopausal Women
Authors: Fenkci Veysel , Yilmazer Mehmet , Alpaslan Mete , Onrat Ersel , Fenkci Semin
Published: July 2003

Objective: To compare the short-term effects of different hormone replacement therapy (HRT) regimens on left ventricular structure and function in healthy postmenopausal women. Methods: Forty-two apparently healthy postmenopausal women were evaluated prospectively in this controlled study. Subjects were divided into 4 groups. Ten subjects, who did not accept HRT or any other treatments, formed the control group. The remaining subjects were assigned to receive oral estradiol (2 mg/day) + norethisterone acetate (1 mg/day) (n = 11), transdermal estradiol (0.05 mg) + norethisterone acetate (0.25 mg) (n = 11) or tibolone (2.5 mg/day) (n = 10) therapy during 12 weeks. Echocardiography and Doppler techniques were used to assess the cardiac effects of different HRT regimens. Results: After 12 weeks of treatment, there were significant increases in left ventricular ejection fraction (transdermal group: p = 0.008, oral group: p = 0.003, tibolone group: p = 0.005) and cardiac output (transdermal group: p = 0.003, oral group: p = 0.003, tibolone group: p = 0.021) in all treatment groups. In addition, in the transdermal group, a slight increase in left ventricular end-diastolic volume was significant (p = 0.046). Conclusion: These data suggest that oral and transdermal HRT regimens and tibolone may contribute to the improvement in left ventricular systolic function without having an effect on left ventricular structure after short-term administration in healthy postmenopausal women.
Maternal Treatment with α-Phenyl-N-tert-Butylnitrone Attenuates Secondary Mitochondrial Dysfunction after Transient Intrauterine Asphyxia in the Fetal Rat Brain
Authors: Taniuchi Yoshinari , Nakai Akihito , Koshino Tatsuo , Araki Tsutomu
Published: July 2003

Recirculation following 30 min of ischemia due to transient uterine artery occlusion in pregnant rats at 20 days gestation has previously been found to cause partial recovery and secondary deterioration of the cellular bioenergetic state in the fetal brain, the subsequent damage being ameliorated by a free radical spin trap agent, α-phenyl-N-tert-butylnitrone (PBN). Our objective was to assess whether the secondary deterioration of the cellular bioenergetic state is due to mitochondrial dysfunction and to study whether PBN acts to prevent secondary damage to mitochondria in the fetal rat brain. Fetal neocortical tissues were sampled after 30 min of intrauterine ischemia and after 1, 2 or 4 h of recirculation. PBN or vehicle was given 1 h after recirculation. Homogenates were prepared, and ADP-stimulated, nonstimulated and uncoupled respiratory rates were measured polarographically. Ischemia was associated with a decrease in ADP-stimulated and uncoupled respiratory rates, with a marked fall in the respiratory control ratio, defined as ADP-stimulated divided by nonstimulated respiration (p < 0.01). Recirculation (1 h) brought about partial recovery, but continued reflow (2 and 4 h) was associated with a secondary deterioration of respiratory functions (p < 0.01). The secondary deterioration was prevented by PBN (p < 0.05). The results demonstrate that the secondary deterioration of the cellular bioenergetic state in ischemia-reperfusion is due to secondary mitochondrial dysfunction and that this deterioration may be induced by oxygen-derived free radicals in the immature fetal brain.
Leptin: A Potential Marker of Placental Insufficiency
Authors: Lepercq Jacques , Guerre-Millo Michèle , André Jocelyne , Caüzac Michèle , Hauguel-de Mouzon Sylvie
Published: July 2003

To investigate placental leptin production in placental insufficiency, placental leptin production was measured in women with severe preeclampsia (group 1) and in normotensive pregnancies associated with intrauterine growth restriction (group 2), compared to controls (group 3). Placental leptin content was increased 3-fold in group 1 compared to group 2 (192.5.1 ± 39.5 vs. 67.8 ± 10.6 ng/g) and 8-fold in group 1 compared to group 3 (192.5.1 ± 39.5 vs. 25.4 ± 6.9 ng/g). Placental leptin content was positively correlated with maternal leptin/BMI ratio (r = 0.62) and the resistance index of the umbilical artery (r = 0.60). These data demonstrate that placental insufficiency is associated with a dramatic increase in placental leptin production. This results in a rise in maternal leptinemia that may be taken as an early index of placental dysfunction.