bluuebunny/crossref_metadata_2025 huggingface dataset:
Tryptophan Metabolism via the Kynurenine Pathway in Experimental Chronic Renal Failure
Authors: Pawlak D. , Tankiewicz A. , Mysliwiec P. , Buczko W.
Published: April 2003

Background: Kidneys are involved in tryptophan (TRP) metabolism in two ways. They eliminate TRP derivatives on the one hand, and they produce several enzymes taking part in TRP metabolism mainly via the kynurenine pathway on the other. The aim of the present study was to examine the time-course of changes in the peripheral kynurenine products degradation during experimental chronic renal failure in rats. Methods: Tryptophan, kynurenine, 3-hydroxykynurenine, kynurenic acid, xanthurenic acid, anthranilic acid and quinolinic acid were determined in plasma using high-performance liquid chromatography technique with UV, fluorescence and electrochemical detection. Results: A decreased TRP level and significant increase in kynurenine pathway metabolite concentrations in plasma of uremic rats were found. Conclusions: Substantial disturbances in the peripheral kynurenic pathway were observed in experimental chronic renal failure. They may contribute to several symptoms of uremia.
Predictors of Deteriorating Cerebral Infarct: Role of Inflammatory Mechanisms. Would Its Early Treatment Be Useful?
Authors: Castillo José , Leira Rogelio
Published: April 2003

The development of neurological deterioration in the hours following the stroke onset occurs in somewhat more than 1 in 3 cerebral infarcts and is associated with an increase in morbidity and mortality. This early deterioration (0–48/72 h) entails the conversion of the ischemic penumbra area in an irreversible lesion, a process that is mediated as much by hemodynamic changes in the local cerebral circulation as by biochemical mechanisms. Late neurological deterioration (3–7 days) is more frequently associated with systemic causes. Knowledge of the various clinical, biochemical and imaging markers associated with neurological deterioration is consequently of fundamental importance. For their repercussion in clinical practice, we classify these predictors of deteriorating cerebral infarct into nonmodifiable, modifiable and possibly modifiable. The reduction in cerebral blood flow in a particular cerebral zone causes very early cerebral damage as a consequence of a significant liberation of neuroexcitatory amino acids, followed by an excessive entry of calcium into the interior of cells; this process causes lipid peroxidation, disintegration of the cellular membranes, nuclear destruction and neuronal death. Moreover, ischemia and posterior reperfusion induce an inflammatory response leading to further cellular destruction. It is therefore conceivable that therapeutic interventions aimed at decreasing proinflammatory cytokines and cell adhesion molecules might result in better outcome in this population.
Thrombolysis in Ischaemic Stroke – Present and Future: Role of Combined Therapy
Authors: Kaste Markku
Published: April 2003

Thrombolysis: ECASS I, the NINDS trial and ECASS II showed that thrombolysis with rt-PA is effective in acute ischaemic stroke. In ECASS I, there was a safety problem because of increased mortality, while the results of the NINDS trial led the FDA to approve the use of rt-PA in ischaemic stroke. The safety was no more a problem in ECASS II. A meta-analysis of those three trials revealed that thrombolysis decreases the risk of death and dependency. For each 1,000 patients treated within 3 h, there will be 140 less dead or dependent, and 90 less if the treatment is given within 6 h. These data support the view that rt-PA should be part of the management of acute ischaemic stroke within 3 h, and probably beyond, in selected patients and experienced centres. Thrombolysis within a 3-hour time frame is also likely to result in net cost savings. Combination Therapy: All trials studying neuroprotecting agents have failed in man, although they have been successful in experimental animals. A combination of thrombolysis and a neuroprotecting agent or a combination of two neuroprotecting agents have been effective in experimental stroke, but the only clinical study with combination therapy (rt-PA with or without lubeluzole) was terminated prematurely before the planned population was enrolled. This was not because of safety problems but because the sponsor lost interest. Conclusion: In future, there will most likely be others to challenge the strategy of the combined therapy, and this strategy will sooner or later lead to a benchmark breakthrough. It is unlikely that any of these therapies or their combinations will work without well-organised services, which can provide fast and efficient medical care. Without such a triage, any drug will be unlikely to have a major impact on stroke recovery.
Evolution of White Matter Lesions
Authors: Schmidt Reinhold , Schmidt Helena , Kapeller Peter , Lechner Anita , Fazekas Franz
Published: April 2003

A 3-year follow-up of 273 participants (mean age 60 years) of the Austrian Stroke Prevention Study provides first information on the rate, clinical predictors and cognitive consequences of MRI white matter lesions (WML) in elderly individuals without neuropsychiatric disease. Lesion progression was found in 17.9% of individuals over a time period of 3 years. Diastolic blood pressure and early confluent or confluent white matter hyperintensities at baseline were the only significant predictors of white matter hyperintensity progression. Genetic association studies in the setting of the Austrian Stroke Prevention Study provide first evidence for genetic susceptibility factors for progression of WML. We observed associations with the paraoxonase Leu→Met 54 polymorphism and with the M235T polymorphism of the angiotensinogen gene. Lesion progression had no influence on the course of neuropsychologic test performance over the observational period, but the statistical power of this analysis was low.
Nomenclature of the Human Immunoglobulin Kappa (IGK) Genes
Authors: Lefranc Marie-Paule
Published: April 2003

‘Nomenclature of the Human Immunoglobulin Kappa (IGK) Genes’, the 17th report of the ‘IMGT Locus in Focus’ section, provides the first complete list of all the human IGK genes. In the most frequent haplotypes, the human IGK locus spans 1,820 kb and the IGKV genes are organized in two clusters separated by 800 kb. In those haplotypes where both the proximal and distal IGKV clusters are present, the total number of human IGK genes per haploid genome is 82 (107 genes if the orphons are included) of which 37–41 are functional. If only the proximal IGKV cluster is present, which is found in a rare haplotype, the total number of genes per haploid genome is 46 (71 genes if the orphons are included) of which 23–25 genes are functional. IMGT/HUGO gene names and definitions of the human IGK genes on chromosome 2p11.2, and IGK orphons on chromosomes 1, 2, 15, and 22 are provided with the gene functionality and the number of alleles according to the rules of the IMGT Scientific chart, with the accession numbers of the IMGT reference sequences, and the accession ID of the Genome Database GDB and NCBI LocusLink databases in which all the IMGT human IGK genes have been entered. The tables are available at the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr:8104) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.
Neurobiological Findings before and during Successful Lithium Therapy of a Patient with 48-Hour Rapid-Cycling Bipolar Disorder
Authors: Voderholzer Ulrich , Weske Gesa , Ecker Sabine , Riemann Dieter , Gann Horst , Berger Mathias
Published: April 2003

48-hour rapid cycling is a very rare form of bipolar disorder, characterized by regular periodic changes of mood from one day to the other. We report on a patient who suffered from a 48-hour rapid cycling without a history of bipolar disorder before the abrupt onset of his rapid mood cycles. We present polysomnographic and neuroendocrine findings and the clinical course based on daily self-ratings of mood. Treatment with lithium carbonate effectively reduced the amplitude of the mood cycles. With plasma levels between 0.8 and 1.0 mmol, almost complete remission occurred. An overview on previous reports on the therapeutic effect of mood stabilizers in this rare form of bipolar disorder is presented.
Acute Exudative Inflammation and Nasally Exhaled Nitric Oxide Are Two Independent Phenomena
Authors: Cervin Anders , Greiff Lennart , Lindberg Sven , Andersson Morgan
Published: April 2003

Background: Increased levels of nitric oxide (NO) and the exudations of plasma proteins to the airway lumen have both been considered characteristics of airway inflammation. The aim of the present study was to investigate a possible relationship between nasal NO concentrations and acutely induced exudative inflammation of the nasal mucosa. Methods: Twelve healthy non-allergic subjects participated. Nasal challenges with saline, histamine 40 µg/ml (H1), histamine 400 µg/ml (H2), oxymethazoline, 0.25 mg/ml (OXY), and a combination of oxymethazoline 0.25 mg/ml and histamine 800 µg/ml (OXYH), were performed on separate occasions. Exhaled NO was measured after each challenge, and α2-macroglobulin (as a marker of plasma exudation) was measured in nasal lavage fluids after the H1 and H2 challenges. Results: The mean baseline NO in all measurements was 164 ± 10.3 ppb. Saline and H1 challenge did not change NO and α2-macroglobulin levels. H2 challenge showed a tendency to reduce NO levels, and the most pronounced decrease was seen after 10 min (–36.3 ± 16.3%, p = 0.07). This reduction was sustained throughout the registration period. Simultanousley with the decrease in NO, α2-macroglobulin levels were increased significantly. OXY challenge alone reduced NO significantly throughout the whole registration period. Maximum decrease was seen at 40 min (–21.3 ± 3.4%, p = 0.03). The OXYH challenge also reduced NO, with a maximal reduction recorded at 10 min (–29.4 ± 6.4%, p = 0.03). The reduction of NO was sustained throughout the registration period (p < 0.01). Conclusion: Histamine 400 µg/ml induced a prompt plasma exudation response whereas a decrease in nasal NO was registered, suggesting that these two events are not necessarily linked. Furthermore it was shown that the vasoconstrictor oxymethazoline reduced nasal NO, which could be related to reduced mucosal blood flow, whereas the reduction of nasal NO after histamine challenge remains to be elucidated.
Bone Wax Foreign Body Granuloma in the Mastoid
Authors: Low W.K. , Sim C.S.
Published: April 2003

The sue of bone wax is commonly used to control bleeding during mastoid surgery. An unusual case of bone wax granuloma in the mastoid, with sigmoid sinus thrombosis, is reported. Although the use of bone wax in and around the mastoid is generally considered safe with few complications, caution should be exercised, particularly in infected fields and in patients known to have general immunohypersensitivity.
Depressive Symptoms in Children and Adolescents with Dysthymic Disorder
Authors: Masi Gabriele , Favilla Letizia , Mucci Maria , Poli Paola , Romano Roberta
Published: April 2003

This report examines clinical features of ‘pure’ dysthymic disorder (DD, without superimposed major depressive disorder, MDD) in a sample of children and adolescents. Profiles of symptomatology and comorbidity as a function of age and gender are described. The sample consisted of 48 subjects (22 males, 26 females, age range 7–18 years, mean age 12.1 years) screened from consecutively referred children and adolescents. All subjects were comprehensively diagnosed with structured diagnostic interviews (Schedule for Affective Disorders and Schizophrenia for School Age, Diagnostic Interview for Children and Adolescents-Revised), according to DSM-IV criteria. Depressed mood, irritability, loss of energy and fatigue, guilt and low self-esteem were present in more than 70% of the subjects. Differences in symptomatic profile between males and females were not significant. Children showed less symptoms than adolescents, but the symptomatic profile was comparable (only anhedonia was significantly more frequent in adolescents). Anxiety disorders were more commonly comorbid with DD, especially separation anxiety disorder in children (33%) and generalised anxiety disorder in adolescents (67%). Externalising disorders were less frequently represented in our sample (14%). An early diagnosis of ‘pure’ DD before the first episode of MDD is crucial for a timely intervention.
The Validity of the ICD-10 Classification of Recurrent Affective Disorders: Do Endogenous and Psychogenic Depressions Form a Homogeneous Diagnostic Group?
Authors: Vetter Peter H. , von Pritzbuer Joachim , Jungmann Karl , Kropp Peter , Köller Olaf
Published: April 2003

Fifty-five hospital-treated patients with the ICD-10 diagnosis of ‘recurrent depressive episode(s)’ were classified according to the Newcastle Depressive Diagnostic Scale as having either psychogenic (n = 25) or endogenous (n = 30) depression and interviewed using several inventories on personality and psychopathology (Composite International Diagnostic Interview, Symptom Check List, Inventory of Interpersonal Problems, IIP, NEO Five-Factor Personality Inventory, Social Adjustment Scale, Questionnaire of the Motivation to Seek Psychotherapy). Except for the IIP, individual subscales disclosed significant differences between the two groups. In light of these results, the grouping of these two disorders into one diagnostic group in the ICD-10 is critically discussed.
Social Cognition and Psychopathology in an Evolutionary Perspective
Authors: Brüne Martin
Published: April 2003

The phylogenetic and ontogenetic developments of social cognition have been a major research focus of evolutionary and developmental psychology. Theory of mind or so-called Machiavellian intelligence, that is the capacity to infer mental states of other individuals and to manipulate them in order to maximise social success, probably emerged due to the need to cope with an increasingly complex social environment. Studies on social reasoning suggest disturbances of mental state attribution in psychiatric disorders. However, apart from autism spectrum disorders, the systematic evaluation of social cognition is still in its infancy, and the present data are ambiguous due to methodological difficulties. Based on the concept of the modular organisation of the mind, a stepwise investigation of social cognition in psychiatric disorders is proposed, including clinical description and available standardised methods. The specific characteristics of psychiatric disorders in respect of social cognition, therefore, may vary according to the hierarchical organisation of the social module. Systematic studies on social reasoning processes in psychiatric disorders may provide new insights also useful for the development of coping strategies in cognitive-behavioural therapy.
Toronto Alexithymia Scale in Outpatients with Sexual Disorders
Authors: Madioni Franca , Mammana Laurent A.
Published: April 2003

The Toronto Alexithymia Scale (TAS-26) was administered to patients with sexual disorders (n = 112) and to healthy control subjects (n = 94). The clinic sample was divided into three subgroups according to DSM-III-R criteria: patients with hypoactive sexual desire disorder (n = 41), patients with orgasm disorders (n = 51) and patients with male erectile disorder (n = 20). TAS scores were significantly higher for male and female patients with hypoactive sexual desire disorder, and with male erectile disorder than controls. The TAS scores in the orgasm disorder patients were not significantly different from those of controls. These results are interesting because they show an association betweeen alexithymia and some sexual symptoms.
Temperament and Disruptive Behavior Disorders
Authors: Schmeck Klaus , Poustka Fritz
Published: April 2003

In several studies on children with conduct disorder, difficult temperament in infancy was one of the major variables in the explanation of later aggressive behavior. According to these studies, subjects with a combination of high novelty seeking, low harm avoidance and low reward dependence (NS high, HA + RD low) should be most at risk for the development of disruptive behavior disorders. The Junior Temperament and Character Inventory was given to a clinical sample of 65 adolescent patients of both sexes with the diagnoses of conduct disorder (with and without attention deficit hyperactivity disorder), emotional disorder (anxiety disorder, obsessive-compulsive disorder, depressive disorder), eating disorder (anorexia, bulimia) or personality disorder (borderline and narcissistic personality disorder). High novelty seeking and low harm avoidance were significantly correlated with externalizing symptoms like aggression and delinquency. In conduct-disordered children and adolescents, we found significantly higher scores of NS compared to the other clinical groups and the normative population, and significantly lower scores of harm avoidance compared to the other clinical groups, but not compared to the normative population. The relative risk of having a conduct disorder was markedly higher in those children and adolescents with elevated scores of novelty seeking.
Influence of Punishment, Emotional Rejection, Child Abuse, and Broken Home on Aggression in Adolescence: An Examination of Aggressive Adolescents in Germany
Authors: Barnow Sven , Lucht Michael , Freyberger Harald-J.
Published: April 2003

The results of this study provide evidence for the importance of psychosocial risks in childhood for aggressive behavior in adolescence. This study demonstrated that aggressive adolescents differed from a nonaggressive control group in an increased exposure to prior psychotraumatic events, such as sexual abuse (tendency), physical abuse, and broken homes. However, in predicting later aggressive behavior, long-term and chronically effective negative living conditions seem of greater importance. Parenting behavior which includes harsh punishment and emotional rejection as well as separation of the parents early in life are particularly important factors. Whereas aggressive girls do not differ from the nonaggressive control group in terms of self-reported mental health, the aggressive boys reported more attention deficits, depression, anxiety, delinquency, and social problems.
Children of Parapartum Mentally Ill Mothers: A Follow-Up Study
Authors: Ruppert Sonja , Bågedahl-Strindlund Margaretha
Published: April 2003

A 2-year cohort of children (n = 75) of hospitalised first-episode parapartum mentally ill mothers in the mid-1970s in Stockholm were studied. The children were followed up during the school-age period from 1982 through 1992, and they were studied with regard to health development, academic achievement and family situation. Comparisons were made with matched controls. Data were collected from hospital case notes, the local tax authorities and school reports. No significant differences were found between the index children and the controls regarding the number of inpatient care episodes or days of inpatient care during the follow-up period. Nor was any significant difference found between the index and the control children regarding academic achievement as measured by the mean of all marks. Four index children and 2 controls were studying in schools for the mentally retarded. Seventy-four percent of the children of the patients were living with their mother, compared to 95% of the controls (p < 0.001). In conclusion, the children of mentally ill mothers in this longitudinal study did as well as the controls. The reason might be the social support provided by society (when needed) for these high-risk families in Sweden.
Coexistence of Delusions of Pregnancy and Infestation in a Male
Authors: Tényi Tamás , Herold Róbert , Fekete Sándor , Kovács Attila , Trixler Mátyás
Published: April 2003

The coexistent appearance of delusions of pregnancy and infestation is reported in a male patient with posttraumatic epilepsy. While published organic cases of delusions of pregnancy have involved patients with severe or mild mental retardation, our reported patient had a higher than average IQ. The interpretative role of these delusions in a probable perceptual symptomatology cannot be excluded, as both delusions can be based on sensations in the abdomen or on the skin.
Recurrent Unipolar Mania in a Psychiatric Hospital Setting in the Fiji Islands
Authors: Aghanwa Henry S.
Published: April 2003

This study aimed to determine the rate of unipolar mania and compare its characteristics with those of other bipolar affective disorders in a psychiatric hospital in the Fiji Islands. Fifty-one patients with unipolar mania seen between January 1999 and October 2000, had their diagnosis confirmed using the Schedules for Clinical Assessment in Neuropsychiatry and the International Classification of Diseases, 10th edition. Their demographic and clinical characteristics were compared with those of 31 manic-depressive patients seen during the period under review. Unipolar mania constituted 47.2% of the bipolar affective disorders in this sample. The frequency of episodes, duration of affective illness, mean age at onset, gender distribution, marital status, employment status and race were not significantly different for the unipolar manic and manic-depressive groups (p > 0.05). Family history of major psychiatric morbidity was 9.8% for the unipolar manic patients and 22.6% for the manic-depressive group (p > 0.05). Recurrent unipolar mania may be considered a useful category based on its high rate, although its demographic and clinical characteristics do not clearly distinguish it from manic-depression.
Therapeutic Interventions Focused on the Family of Bipolar Patients
Authors: Reinares M. , Colom F. , Martínez-Arán A. , Benabarre A. , Vieta E.
Published: April 2003

Background: Although genetic and biological factors are crucial in the pathophysiology of bipolar disorder, the importance of psychosocial and familial factors in triggering or mitigating relapses warrants the implementation of psychotherapeutic interventions. The authors review and criticize the role of family intervention in bipolar disorder. Methods: The main computerized databases (Medline, Psychological Abstracts, Current Contents) have been searched for the terms ‘family intervention’, ‘family management’, ‘family therapy’, ‘psychotherapy’, ‘psychoeducation’ and ‘bipolar disorder’. Results: Some studies have associated high expressed emotion in relatives and poorer outcome in bipolar disorder. Studies on families of bipolar patients seem to support that family intervention as adjunctive therapy to pharmacological treatment may reduce the number of relapses and hospitalizations, improving familial, occupational and social functioning. However, controlled studies are scarce and most of them have a great number of methodological pitfalls such as small sample size, uncontrolled pharmacological treatment, absence of long follow-up and biased populations, among others. Conclusions: Both bipolar patients and their relatives could benefit from family intervention as adjunctive treatment to pharmacotherapy. Nevertheless, it would be necessary to design further investigations avoiding some of the limitations listed above, and controlling additionally for psychopathology in family members, and the influence of life events. It would be important to distinguish between causes and effects, studying which factors are involved in family attitudes and determining whether the interactive patterns are variable or stable according to the clinical state of the patient. Finally, it would be useful to design viable, effective and measurable interventions for the accurate delimitation of the role of family intervention in the treatment of bipolar disorder.
Psychological Mediation of a Type of Oxidative DNA Damage, 8-Hydroxydeoxyguanosine, in Peripheral Blood Leukocytes of Non-Smoking and Non-Drinking Workers
Authors: Irie Masahiro , Asami Shinya , Nagata Shoji , Miyata Masakazu , Kasai Hiroshi
Published: April 2003

Background: The present study investigates whether the formation of 8-hydroxydeoxyguanosine (8-OH-dG), a known oxidative DNA damage relevant to carcinogenicity, can be associated with psychological factors, in order to clarify the possible stress-cancer linkage from a genetic viewpoint. Methods: We performed a cross-sectional study in which we examined the relationships of the levels of 8-OH-dG in peripheral blood leukocytes to various psychological factors, including the Profile of Mood States (POMS) and the Center for Epidemiologic Studies Depression Scale (CES-D) in 38 non-smoking and non-drinking workers (19 males and 19 females). Results: The levels of 8-OH-dG in male subjects were negatively correlated with the Tension-Anxiety scores of the POMS. In contrast, the levels of 8-OH-dG in female subjects were positively correlated with the Depression-Rejection scores of the POMS and the CES-D scores, and negatively associated with the Vigor scores of the POMS, respectively. Male subjects who had self-blame coping strategy displayed significantly high levels of 8-OH-dG. Moreover, the worse the subjective closeness to parents in childhood, the higher the levels of 8-OH-dG became in male subjects. The levels of 8-OH-dG increased reliably in subjects who had experienced the loss of a close family member within 3 years, when compared with non-bereaved subjects. Conclusions: Psychological distress may be associated with cancer risk, although sex difference influences them. Inadequate coping styles, possibly resulting from a poor interpersonal relationship with parents since childhood, and experience of a relatively recent loss of a close family member also appear to influence the pathogenesis of cancer.
Surfactant Replacement for Ventilator-Associated Pneumonia: A Preliminary Report
Authors: Baughman Robert P. , Henderson Rogene F. , Whitsett Jeffrey , Gunther Karen L. , Keeton Deborah A. , Waide James J. , Zaccardelli David S. , Pattishall Edward N. , Rashkin Mitchell C.
Published: April 2003

Background: Surfactant abnormalities have been described in bacterial pneumonia. Objective: To determine the safety and effect of exogenous surfactant replacement in patients with ventilator-associated pneumonia (VAP). Methods: Patients with VAP were randomized in a double-blind study to receive either an artificial surfactant (Exosurf) consisting mostly of disaturated phospholipids (DSPL) or saline via a continuous nebulizer system for 5 days. Patients underwent bronchoscopy and bronchoalveolar lavage (BAL) prior to and after 4 days of therapy. Results: Twenty-two patients were randomized, with 8 receiving Exosurf. There was no detected difference in outcome between the saline- and Exosurf-treated patients in terms of days on ventilator, 30-day or hospital mortality. At the follow-up lavage, the patients treated with Exosurf had a significant rise in the level of DSPL (p < 0.05), while the saline group did not, suggesting delivery of drug. Also at the follow-up lavage, the percentage of neutrophils in the BAL fell in the Exosurf patients (p < 0.01), but not in the saline group. Conclusion: Exogenous surfactant replacement given to patients with VAP increased the amount of DSPL retrieved by BAL. This treatment was associated with a fall in the neutrophil response to pneumonia.
Approaching Tolerance in Transplantation
Authors: Waldmann Herman , Cobbold Stephen
Published: April 2003

Basic research has provided substantial encouragement that tolerance processes may be harnessed to the benefit of organ transplants. The goal of achieving mixed chimerism to ensure a robust tolerance, however elegant, may yet prove to be too complex and, consequently, risky as a procedure to compensate for the breadth of genetic differences, and prior immunological experiences of donor and host. Tolerance through regulation may prove to be easier to generate, but insufficiently robust to maintain. In the end the chosen protocol will be one that is simple, cheap and can guarantee patient compliance. Pragmatically, such a protocol need not be one aimed at clear-cut drug-free tolerance, but rather one which is trouble free. This could end up as a combination of partial tolerance (where tolerance processes have been harnessed) induced through a short-term treatment, in conjunction with easily tolerated maintenance therapy with select immunosuppressive drugs. Perhaps to the patient, the holy grail of tolerance is not as important as the complete assurance that the graft will survive and continue to function in all circumstances.
Melatonin and β-Endorphin Changes in Children Sensitized to Olive and Grass Pollen after Treatment with Specific Immunotherapy
Authors: Girón-Caro F. , Muñoz-Hoyos A. , Ruiz-Cosano C. , Bonillo-Perales A. , Molina-Carballo A. , Escames G. , Macías M. , Acuña-Castroviejo D.
Published: April 2003

Background: Specific immunotherapy for respiratory allergy, a seasonal disease, significantly reduces the inflammatory process, attenuating the clinical symptoms. The mechanism for the clinical beneficial effect of immunotherapy has not yet been clarified. Melatonin shows a circadian and seasonal variation and together with the endogenous opioid system plays an immunomodulatory role acting on both specific and nonspecific immunity responses. Thus, the possibility that immunotherapy involved changes in the melatonin-opioid system was investigated. Methods: Thirty-five children aged 3–15 years with rhinitis and asthma due to olive + grass pollen sensitization were studied. The patients were treated with depot extracts containing the identified allergens with increasing doses from 1 to 1,000 IU/ml during 3 months. Melatonin, β-endorphin, total and specific IgE and IgG4 were determined before and after treatment. Results: All children showed a significant improvement of their symptoms at the end of the treatment, coinciding with a significant drop of both melatonin and β-endorphin levels. Total IgE decreased in most of the cases although the mean values did not show significant changes. Specific IgE and IgG4 were also unchanged. A significant correlation between melatonin and β-endorphin and between β-endorphin and IgG4 was found before immunotherapy, and these correlations disappeared when the treatment was finished. Conclusions: The decrease in the levels of melatonin and β-endorphin suggests the disappearance of their stimulating influence on the immune system. Thus, hyposensitization after immunotherapy may involve, at least in part, the inhibition of the immunoenhancing properties of the melatonin-opioid system.
The Role of Interleukin 10 in the Regulation of Allergic Immune Responses
Authors: Bellinghausen Iris , Knop Jürgen , Saloga Joachim
Published: April 2003

Several clinical studies and animal models have shown that Th2 lymphocytes play a key role in the pathophysiology of IgE-mediated allergic immune responses like allergic rhinitis and asthma or venom anaphylaxis. Classical specific immunotherapy (SIT) that has been proven to be clinically effective can serve as a role model for immunological changes that are associated with amelioration of allergic diseases. During SIT, the Th2-dominated immune response is modified towards a Th1 response leading to a decline in allergen-specific IgE and an increase in allergen-specific IgG production. Most importantly, however, production of the immunosuppressive/-regulatory cytokine interleukin 10 (IL-10) is also induced leading to T cell tolerance and prevention of tissue inflammation. In this article the role of IL-10-producing T cells in the regulation of allergic immune responses will be discussed.
IgE and IgG Binding Epitopes on α-Lactalbumin and β-Lactoglobulin in Cow’s Milk Allergy
Authors: Järvinen Kirsi-Marjut , Chatchatee Pantipa , Bardina Ludmilla , Beyer Kirsten , Sampson Hugh A.
Published: April 2003

Background: Cow’s milk is one of the most common causes of food allergy in the first years of life. We recently defined IgE and IgG binding epitopes for αs1-casein, a major cow’s milk allergen, and found an association between recognition of certain epitopes and clinical symptoms of cow’s milk allergy (CMA). Since α-lactalbumin (ALA) and β-lactoglobulin (BLG) are suspected to be significant allergens in cow’s milk, we sought to determine the structure of sequential epitopes recognized by IgE antibodies to these proteins. We further sought to assess the pattern of epitope recognition in association with the clinical outcome of CMA. Methods: According to the known amino acid sequence of ALA and BLG, 57 and 77 overlapping decapeptides (offset by two amino acids), respectively, were synthesized on a cellulose derivatized membrane. Sera from 11 patients 4–18 years of age with persistent CMA (IgE to cow’s milk >100 kUA/l) were used to identify IgE binding epitopes. In addition, 8 patients <3 years of age and likely to outgrow their milk allergy (IgE to cow’s milk <30 kUA/l) were used to investigate the differences in epitope recognition between patients with ‘persistent’ and those with ‘transient’ CMA. Seven patients 4–18 years of age were used for assessing the IgG binding regions. Results: In patients with persistent allergy, four IgE binding and three IgG binding regions were identified on ALA, and seven IgE and six IgG binding epitopes were detected on BLG. The younger patients that are likely to outgrow their allergy recognized only three of these IgE binding epitopes on BLG and none on ALA. Conclusions: The presence of IgE antibodies to multiple linear allergenic epitopes may be a marker of persistent CMA. The usefulness of IgE binding to distinct epitopes on whey proteins in defining the patients that would have a lifelong CMA needs to be investigated in further studies.
Identification of IgE-Binding Proteins in Soy Lecithin
Authors: Gu Xuelin , Beardslee Tom , Zeece Michael , Sarath Gautam , Markwell John
Published: April 2003

Background: Soy lecithin is widely used as an emulsifier in processed foods, pharmaceuticals and cosmetics. Soy lecithin is composed principally of phospholipids; however, it has also been shown to contain IgE-binding proteins, albeit at a low level. A few clinical cases involving allergic reactions to soy lecithin have been reported. The purpose of this investigation is to better characterize the IgE-binding proteins typically found in lecithin. Methods: Soy lecithin proteins were isolated following solvent extraction of lipid components and then separated on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The separated lecithin proteins were immunoblotted with sera from soy-sensitive individuals to determine the pattern of IgE-binding proteins. The identity of IgE-reactive bands was determined from their N-terminal sequence. Results: The level of protein in six lecithin samples obtained from commercial suppliers ranged from 100 to 1,400 ppm. Lecithin samples showed similar protein patterns when examined by SDS-PAGE. Immunoblotting with sera from soy-sensitive individuals showed IgE binding to bands corresponding to 7, 12, 20, 39 and 57 kD. N-terminal analysis of these IgE-binding bands resulted in sequences for 3 components. The 12-kD band was identified as a methionine-rich protein (MRP) and a member of the 2S albumin class of soy proteins. The 20-kD band was found to be soybean Kunitz trypsin inhibitor. The 39-kD band was matched to a soy protein with unknown function. Conclusions: Soy lecithin contains a number of IgE-binding proteins; thus, it might represent a source of hidden allergens. These allergens are a more significant concern for soy-allergic individuals consuming lecithin products as a health supplement. In addition, the MRP and the 39-kD protein identified in this study represent newly identified IgE-binding proteins.
Atopic Dermatitis-Like Skin Lesions Induced by Topical Application of Mite Antigens in NC/Nga Mice
Authors: Sasakawa Tatsuya , Higashi Yasuyuki , Sakuma Syozo , Hirayama Yoshitaka , Sasakawa Yuka , Ohkubo Yoshitaka , Goto Toshio , Matsumoto Masahiro , Matsuda Hiroshi
Published: April 2003

Background: Atopic dermatitis (AD) is a chronic relapsing inflammation usually observed in patients with an individual or a familial history of atopic diseases, precipitated by environmental factors including mite antigens (Ag). However, the exact etiology of AD is unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is necessary. In this study, we developed a new animal model of AD induced by mite Ag in NC/Nga mice. Methods: We injected the extracts of mite Ag intradermally at the ventral side of the ear of SPF NC/Nga mice on days 0, 2, 4, 7, 9, 11, 14 and 16, and measured the clinical symptoms and the ear thickness. On day 18, we collected blood and submandibular lymph nodes (LN) of the immunized ear to perform a histochemical analysis, and to measure the plasma immunoglobulins and cytokines. Results: The NC/Nga mice immunized with mite Ag suffered from AD-like skin lesions including erythema followed by edema, excoriation and scaling. The histological and immunohistochemical examinations of the affected skin showed epidermal hyperplasia with hyperkeratosis, severe infiltration of CD4+ T lymphocytes, eosinophils and macrophages, and degranulation of mast cells. The total plasma IgE level was markedly elevated in mite Ag-treated mice. LN cells of mice immunized with mite Ag synthesized IgE in an Ag-dependent manner and secreted interleukin-4 (IL-4) and IL-5 but not interferon-γ. Conclusions: NC/Nga mice treated with mite Ag manifest clinical and immunological aspects similar to patients with AD, suggesting that this model is suitable for exploring the pathogenesis of human AD.
Highly Active Antiretroviral Therapy Responders Exhibit a Phenotypic Lymphocyte Pattern Comparable to That of Long-Term Nonprogressors
Authors: Knapp Sylvia , Lenz Petra , Gerlitz Sabine , Rieger Armin , Meier Susanna , Stingl Georg
Published: April 2003

Background: The implementation of highly active antiretroviral therapy (HAART) in patients with progressive HIV-1 disease has resulted in a marked reduction of HIV-1-associated morbidity and mortality. In fact, the risk of HAART responders to develop opportunistic infections becomes similar to that of long-term nonprogressors (LTNPs). Methods: Reasoning that HAART may ultimately have consequences on both the quantity and quality of immune responses of a HIV-1-infected person, we assessed CD4+ and CD8+ T cell subsets in HAART recipients over a time period of 15 months and compared them to the lymphocyte phenotype of LTNPs and healthy controls. Evaluations included quantitative determinations of memory (CD45RO+CD62L–), naive (CD45RO–CD62L+), effector (CD27–, CD28–) and activated (HLA-DR+, CD38+, CD95+) CD4+ and CD8+ lymphocytes. The T cell function was assayed by skin tests. Results: Compared to healthy persons, treatment-naive patients with progressive disease exhibited a considerable reduction of CD4+ T cells with many of the remaining T cells showing signs of activation at baseline. CD8+ T cells were greatly increased in number, mainly because of an expansion of CD28– effector and memory CD8+ T cells. LTNPs, in contrast, had stable CD4+ and elevated CD8+ T cell counts, the latter being mainly due to a marked increase in CD27– effector cells. Essentially, the same immunophenotype was seen in HAART responders after 15 months of treatment when compared to LTNPs. Conclusions: It is tempting to speculate that a HAART-induced reduction in viral load may influence the immune system’s capacity to mount protective responses to pathogenic microorganisms.
Gene Expression Profiling in Immune Cells Using Microarray
Authors: Granucci Francesca , Castagnoli Paola Ricciardi , Rogge Lars , Sinigaglia Francesco
Published: April 2003

The recent development of DNA microarray, which offers the opportunity to study the expression of thousands of individual genes simultaneously in different biological systems, has provided new insights into the immune system. Examples discussed in this review include molecular descriptions of the differentiation program of T helper (Th) cells into Th1 and Th2 pathways and the genetic program underlying maturation of dendritic cells. It is anticipated that this new information can be used to understand gene function in both physiological and pathological conditions of the immune system.
The Effect of Leukotriene D4 Inhalation on the Antigen-Induced Airway Hyperresponsiveness and Inflammation in 5-Lipoxygenase Gene-Deficient Mice
Authors: Kawada Naoki , Yamada Takatoshi , Takahashi Yoshimasa , Tokuoka Shouta , Masuda Taisei , Tanaka Hiroyuki , Nagai Hiroichi
Published: April 2003

Background: The role of 5-lipoxygenase (5-LO) products in the asthmatic bronchoconstriction is evident. However, the role of 5-LO products in airway hyperresponsiveness (AHR) and airway inflammation is still under discussion. The aim of the present study is to investigate the role of leukotriene D4 (LTD4) in AHR and allergic airway eosinophilia in mice. Methods: The effect of LTD4 inhalation on antigen-induced AHR and airway eosinophilia was investigated in 5-LO gene-deficient mice. Results: After three inhalations of LTD4, airway responsiveness to acetylcholine was not altered in normal or allergic wild-type and 5-LO knockout (KO) mice. In contrast, the number of eosinophils in 5-LO KO allergic mice increased to the level of wild-type allergic mice after the inhalation of LTD4. These observations were confirmed by a histopathological study of the lungs. No change in the cytokine levels in bronchoalveolar lavage fluid and serum immunoglobulin levels was shown after LTD4 inhalation. Conclusion: These findings suggest that LTD4 plays a role in eosinophilic airway inflammation but not in AHR in mice.
Angiogenic Effects of Suture Biomaterials
Authors: Foschi D. , Corsi F. , Cellerino Paola , Rizzi A. , Morandi E. , Trabucchi E.
Published: April 2003

Angiogenesis is a limiting step of inflammation and wound healing. Although laboratory tests for the evaluation of the angiogenetic effects of biomaterials are available, no investigations have been performed. In this study we examine the angiogenetic effect of suture biomaterials in the rat mesenteric window model. Absolute controls had laparotomy only, controls had mesenteric window wounding, test groups had the insertion of either a thread of collagen, polyglactin 910, polyglycolic acid salt, silk or of a titanium clip. We considered the percentage area of the mesenteric window covered by neovessels. After 7 days, negligible angiogenesis was found in absolute controls, significant angiogenesis in controls, collagen, polyglactin 910 and polyglycolic acid salt treated rats, without differences between treatments. A significant increase of angiogenesis in comparison to the control group was found in rats treated with silk and titanium. Ultramicroscopy of the neovessels showed specific changes of their architecture in titanium-treated rats. In conclusion, angiogenesis during wound healing is differently influenced by the suture material used. Silk and titanium stimulated angiogenesis in a different way.
Mitochondrial ATP-Sensitive Potassium Channel Plays a Dominant Role in Ischemic Preconditioning of Rabbit Heart
Authors: Nakai Y. , Horimoto H. , Mieno S. , Sasaki S.
Published: April 2003

Background: The ATP-sensitive potassium (KATP) channel has been shown to be important in the ischemic preconditioning (IPC) response. Recently, the mitochondrial rather than the sarcolemmal KATP channel has been focused on due to its energy-modulating property. Hence, this study was undertaken to elucidate the role of the mitochondrial KATP channel in IPC by modulating the mitochondrial KATP channel in isolated perfused rabbit hearts. Methods: Seven hearts served as a control with no interventions. Seven hearts underwent IPC consisting of two 5-min cycles of global ischemia followed by 5 min of reperfusion. Seven hearts received the selective mitochondrial KATP channel blocker 5-dehydroxydecanoate (5-HD, 100 µM) for 5 min before IPC, and 7 hearts received the selective mitochondrial KATP channel opener diazoxide (50 µM) for 5 min. Then, all hearts were subjected to 1 h of left anterior descending coronary artery ischemia and 1 h of reperfusion. Left ventricular pressures, monophasic action potentials and coronary flow were measured throughout the experiment and infarct size was detected at the end of experiment. Results: (1) The mitochondria-selective KATP channel opener diazoxide reduced infarct size as compared to control (p < 0.05); (2) IPC reduced infarct size and preserved postischemic diastolic function as compared to control (p < 0.05), and (3) the mitochondria-selective KATP channel blocker 5-HD reversed these effects. Conclusion: The mitochondrial ATP-sensitive potassium channel may be a potential site of cardioprotection.
Expression of PDGF-A, TGFb and VCAM-1 during the Developmental Stages of Experimental Atherosclerosis
Authors: Misiakos E.P. , Kouraklis G. , Agapitos E. , Perrea D. , Karatzas G. , Boudoulas H. , Karayannakos P.E.
Published: April 2003

Purpose: A considerable number of growth factors, cytokines, and adhesion molecules are implicated in the development of atherosclerotic lesions. These molecules interact in a complex network influencing the evolution of several processes, such as lipid metabolism, cellular proliferation and tissue repair. The aim of this study was to evaluate the expression of the growth factors PDGF-A, and TGFb, and the adhesion molecule VCAM-1 in the sequential steps of experimental atherogenesis. Methods: Forty-two New Zealand white male rabbits were divided into 4 groups. The group A rabbits (n = 8) received normal diet and served as control animals. The remaining groups were fed with a diet enriched with 1% cholesterol and 6% corn oil. The rabbits of group B (n = 9) were sacrificed 1 month after the beginning of the study, of group C (n = 15) after 2 months and of group D (n = 10) after 3 months. In tissue sections of the aortic arch the antibodies of the prementioned factors were detected immunohistochemically. Results: In group A only TGFb and PDGF-A were detectable. In lesions of the first month PDGF-A expression was high but declined towards the third month. VCAM-1 expression was getting more intense up to the second month and subsided thereafter. TGFb expression intensified towards the third month. Changes in the expression of these factors were statistically significant. Conclusion: PDGF-A, responsible for the uncontrollable growth of smooth muscle cells, and VCAM-1, regulating monocyte recruitment in the intima, acts mainly during the early stages of atherogenesis. TGFb, one of the main factors controlling the formation of connective tissue matrix, has a gradually increasing expression towards the third month contributing probably to the fibrous plaque formation.
Multiple Breeding Females in Captive Groups of Golden-Headed Lion Tamarins (Leontopithecus chrysomelas): Causes and Consequences
Authors: De Vleeschouwer Kristel , Van Elsacker Linda , Leus Kristin
Published: April 2003

In Callitrichidae, reproduction in subordinate females is generally inhibited but occurs in rare cases, possibly in association with the presence of an unrelated male, important food resources or low dispersal opportunities. This study investigates the occurrence of groups with multiple breeding females in captive golden-headed lion tamarins (Leontopithecus chrysomelas), the factors leading to their formation and the consequences for the group. Information obtained from studbook data on the world captive population during 1984–1998 revealed that polygynous groups in captivity are very rare: only 7 cases were discovered. Family groups in which daughters started breeding with a related male were larger than average, had a high number of sexually mature sons and eldest offspring that were well past the age of sexual maturity. Following a breeding attempt, severe aggression frequently occurred, especially if the infants were liveborn. Polygynous groups composed of two related females and an unrelated male tended to remain stable for a longer period than families with breeding daughters. Competition for infant care is probably an important factor determining whether the polygynous situation can persist and for how long.