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Monoclonal antibodies cross-reactive with group A streptococci and normal and psoriatic human skin.

Infection with group A streptococci has been implicated as a factor capable of exacerbating psoriasis. In order to explore the possibility of cross-reactivity between streptococcal antigens and human skin in this phenomenon, skin from psoriatic patients and control subjects was reacted with 3 monoclonal antibodies against group A streptococci and antibody binding was estimated by the indirect immunofluorescence technique. Monoclonal antibody 54.2.8 stained the nuclei and cytoplasm of cells within the epidermis and epidermal appendages, as well as cells scattered throughout the dermis. In contrast, monoclonal antibodies 49.8.2 and 36.2.2 labeled the cytoplasm of epidermal cells and epidermal appendages but did not react with nuclei. No difference in the staining patterns of control skin and uninvolved skin from patients with psoriasis was observed. However, skin from psoriatic lesions contained large amounts of cross-reactive skin component(s). Sera from patients with guttate psoriasis did not react differently with normal or psoriatic skin when compared with normal sera. Western immunoblots of skin extracts demonstrated that monoclonal antibody 54.2.8 reacted with a family of proteins in the molecular weight range of 60-70K. The results indicate that component(s) in human skin share cross-reactive epitopes with group A streptococci. Immunologic cross-reactions between group A streptococci and human skin may play an important role in the exacerbation of certain skin disorders following streptococcal infections.

Adolescent↗

Childhood non-Hodgkin's lymphoma developing from recurrent neck mass.

Non-Hodgkin's lymphoma (NHL) in an 8-year-old boy developing from recurrent neck mass during 15-months history is presented. Two biopsies carried out during this period were interpreted as reactive change. The third biopsy was diagnosed as NHL. He died of the systemic disease 19 months after the first admission. Clinical, histological and immunocytochemical investigations for the three biopsy materials revealed that the first and the second biopsies were reactive, and the third biopsy was neoplastic, B cell lymphoma. Known etiological factors causing lymphoreticular disorders are reviewed by the literatures, and absence of these factors in the present case is described.

B-Lymphocytes↗

Fine needle aspiration cytology and immunocytochemical characterization of the histiocytes in sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman syndrome).

A fine needle aspiration (FNA) biopsy of an enlarged lymph node in a three-year-old boy who had asymptomatic cervical and submandibular lymphadenopathy showed large histiocytes with abundant pale, eosinophilic cytoplasm containing well-preserved lymphocytes and occasional plasma cells and granulocytes. These features were consistent with a diagnosis of sinus histiocytosis with massive lymphadenopathy (SHML). Immunophenotypic study of the histiocytes, performed on the FNA smears and on paraffin-embedded sections, showed reactivity for S-100 protein and alpha-1-antichymotrypsin and negativity for lysozyme. These features, which are characteristic of SHML, demonstrate the reliability of FNA cytology in making the diagnosis of this disorder.

Biomarkers↗

Cellular immunity in newborn infants and children: stimulation of lymphocyte protein synthesis as a measure of immune competence.

An assay based on the early stimulation of protein synthesis in lymphocytes has been used as an in vitro measure of cellular immune competence. 3H-labelled leucine incorporation into human peripheral lymphocytes (PBL) stimulated by the mitogens phytohaemagglutinin (PHA), wax bean agglutinin (WBA) and Concanavalin A (Con A) was measured after one day in culture. This assay offers a technical advantage over the analogous 3H-labelled thymidine incorporation assay, because of the short incubation time required and the absence of homologous serum in the assay system. Newborn infants and patients with Down's syndrome as a group had normal responses, whereas those suffering from recurrent infections demonstrated normal or hyper-reactive responses. Patients with lymphoproliferative disorders, ataxia telangiectasia, and some patients under steroid therapy had diminished immune proliferative reactions. These results are in agreement with most previously reported studies using other assay systems.

Adolescent↗

The role of early adverse experience and adulthood stress in the prediction of neuroendocrine stress reactivity in women: a multiple regression analysis.

Sensitization of stress-responsive neurobiological systems as a possible consequence of early adverse experience has been implicated in the pathophysiology of mood and anxiety disorders. In addition to early adversities, adulthood stressors are also known to precipitate the manifestation of these disorders. The present study sought to evaluate the relative role of early adverse experience vs. stress experiences in adulthood in the prediction of neuroendocrine stress reactivity in women. A total of 49 women (normal volunteers, depressed patients, and women with a history of early abuse) underwent a battery of interviews and completed dimensional rating scales on stress experiences and psychopathology, and were subsequently exposed to a standardized psychosocial laboratory stressor. Outcome measures were plasma adrenocorticotropin (ACTH) and cortisol responses to the stress test. Multiple linear regression analyses were performed to identify the impact of demographic variables, childhood abuse, adulthood trauma, major life events in the past year, and daily hassles in the past month, as well as psychopathology on hormonal stress responsiveness. Peak ACTH responses to psychosocial stress were predicted by a history of childhood abuse, the number of separate abuse events, the number of adulthood traumas, and the severity of depression. Similar predictors were identified for peak cortisol responses. Although abused women reported more severe negative life events in adulthood than controls, life events did not affect neuroendocrine reactivity. The regression model explained 35% of the variance of ACTH responses. The interaction of childhood abuse and adulthood trauma was the most powerful predictor of ACTH responsiveness. Our findings suggest that a history of childhood abuse per se is related to increased neuroendocrine stress reactivity, which is further enhanced when additional trauma is experienced in adulthood.

Adrenocorticotropic Hormone↗

Repetitive behaviors in autistic disorder.

INTRODUCTION: Repetitive behaviors are common in autistic disorder, as in other developmental disabilities. Behaviors as diverse as stereotypies, cognitive inflexibility, and a need for sameness are grouped together under DSM IV classification, even though they are diverse in phenomenology, underlying neural circuitry, and possible clinical significance. In order to better define repetitive behaviors, we studied the relationship between such behaviors and chronological age, developmental level, estimated IQ, presumed mood state, severity of illness, as well as behavior reactivity to environmental stimuli, in a group of 121 consecutive autistic children, aged 2-4 and 7-11 years. RESULTS: Younger autistic children displayed more motor and sensory repetitive behaviors. Older children had more complex behaviors. Children with higher IQ scores, likewise, demonstrated more complex repetitive behaviors. Most motor behaviors and self injury showed features of reactivity. CONCLUSIONS: Certain "repetitive" activities may not represent core features of autistic disorder and may be equivalent to normal motor and cognitive behaviors, as seen during typical development.

Age Factors↗

Hormonal and behavioral homeostasis in boys at risk for substance abuse.

This study modeled the influences of cortisol reactivity, androgens, age-corrected pubertal status, parental personality, family and peer dysfunction on behavioral self-regulation (BSR), in boys at high (HAR) and low average risk (LAR) for substance abuse. Differences between risk groups in cortisol and androgen concentrations, and cortisol reactivity were also examined. Subjects were 10- through 12-year-old sons of substance abusing fathers (HAR; n = 150) and normal controls (LAR; n = 147). A multidimensional construct of BSR was developed which utilized multiple measures and multiple informants. Boys reported on family dysfunction and deviant behavior among their peers. Parents reported on their propensity to physically abuse their sons, and their own number of DSM-III-R Antisocial Personality Disorder symptoms. Endocrine measures included plasma testosterone, dihydrotestosterone, and salivary cortisol. HAR boys, compared to LAR boys, had lower mean concentrations for testosterone, dihydrotestosterone, salivary cortisol prior to evoked related potential testing, and lower cortisol reactivity. The number of maternal Antisocial Personality Disorder symptoms, parental potential for physical abuse, degree of family dysfunction, and peer delinquency were significantly associated with BSR. Parental aggression antisocial personality symptoms and parental physical abuse potential are likely to influence sons' behavioral dysregulation and homeostatic stress reactivity. These key components of liability are posited to increase the likelihood of developing suprathreshold Psychoactive Substance Use Disorder (PSUD).

Antisocial Personality Disorder↗

Anxiety of the 8th month in the preterm child.

BACKGROUND: Aim of this paper was to verify whether the condition described by Spitz as anxiety of the 8th months occurs earlier in the preterm than in the child born at term. METHODS: A prospective study was carried out on 27 subjects subdivided into three groups of 9, 8, 10 patients, respectively, according to gestational age (group I < or = 33 weeks; group II > or = 34 < or = 37 weeks; group III > or = 38 < or = 41 weeks). The cases were selected at random from the patients admitted to the Neuropsychomotor Unit of the Gaslini Institute of Genoa (Italy), from May 1, 1993 to May 22, 1998. All 27 subjects underwent regular follow-up according to the protocol adopted in the Unit. RESULTS: It was observed that in group I (very preterm children), this type of anxiety had a much earlier onset with respect to group II (preterm children with higher gestational age) and III (children bom at term), in which time of onset was similar. CONCLUSIONS: This observation could be ascribed i) to the peculiar organic and emotional conditions of a very preterm infant, who therefore is more "reactive", and ii) to its inborn ability to react promptly with manifestations of sudden alarm of fear within the frame work of interpersonal contacts.

Anxiety↗

[Clinical guide scale for the developmental stages of treated autism].

An evolutionary diagram that takes into account the development of personality and its structuring or restructuring was developed thanks to a better understanding of autistic disorders from a psychodynamic point of view through long term psychoanalytic treatment of autistic children. This grid is organised around the major stages of the formation of the bodily ego which autistic children helped us understand better. The construction of space and the capacities of cognitive instrumentation are logically within this line of structuring. These major stages are defined: the first is the "successful" autistic state; the second is the stage where the primary skin is recovered (feeling of a circular envelope); the third is the symbiotic phase which includes vertical splitting then horizontal splitting of the image of the body; finally, the fourth is the phase of individuation/separation into a whole body. At each stage the following are assessed: state of the image of the body, of the gaze, of language, of writing, the autistic symptoms, emotional-relational manifestations, exploration of space and objects, recognition in time, the aggressive behaviours, reactivity to pain and to immune states (somatic and psychosomatic manifestations).

Autistic Disorder↗

Oxidative stress in children with kidney disease.

The aim of this work was to study the dynamics of oxidative stress in the blood and urine of children with kidney diseases: glomerulonephritis (GN), pyelonephritis (PN), renal failure (RF), and lower urinary tract infections (LUTI). The concentration of conjugated dienes is increased in blood: GN 4 times and RF up to 2 times; and extremely increased in urine: GN 12 times and RF 4 times. The concentration of thiobarbituric acid reactive substances in urine shows a similar trend: GN 7 times, PN 2 times, RF 1.5 times, and LUTI almost 3 times. Urine chemiluminescence is also increased: GN 5 times, PN and LUTI 3 times, and RF 6 times. Kidney disease leads to 2.5-fold inhibition of antioxidant catalase activity in blood and 10-fold in urine. Total antioxidant activity of urine is induced in all groups: GN 18 times, PN 2 times, RF 1.5 times, and almost 4 times in the LUTI group. Experimental data confirm that products of lipid peroxidation, intensity of chemiluminescence, and total and enzyme antioxidant capacity in combination with clinical parameters are a proper test for the dynamics of oxidative stress and markers of intoxication in children with inflammatory and immunological active parenchymal kidney disorders. These data could be helpful for the optimization of complex and effective antioxidant therapy of children with kidney disease.

Adolescent↗

Structural variants of human growth hormone: biochemical, genetic, and clinical aspects.

Human growth hormone (hGH) is a mixture of peptides in which the major physiologic component is a single chain polypeptide of 191 residues with a molecular weight of 22,000 ("22K" form). The minor components differ from the 22K form in terms of mass (e.g. the 20K form, a single-chain peptide synthesized by deletion of residues 32-46 of the 22K isomer, and the 45K variant formed by aggregation of the 22K molecule), or of charge (e.g. the more acidic two-chain forms alpha 2 and alpha 3 which are generated by proteolytic deletion of residues 135-140 and 135-146 from the 22K variant). The minor components also differ from the 22K molecule in (a) their metabolic effects; (b) their capacity to bind to antiserum raised against the 22K form in a radioimmunoassay (RIA); and (c) their ability to bind to membrane receptors for the 22K hGH in a radioreceptor assay (RRA). Two genes, N and V, involved in the biosynthesis of hGH, are located on human chromosome 17. Heritable alterations of the N gene may cause deficiency of immunoreactive hGH and growth failure. A pathologic variant of hGH has also been identified which is indistinguishable from the 22K form on RIA, but which has low reactivity on hGH-RRA and low somatomedogenic activity. Several mechanisms to account for this bioinactive variant are discussed.

Child↗

[Possible disorder of tissue immunity function in mothers who have given birth to a child with Down's disease].

The rates of DNA synthesis were studied in PHA-stimulated lymphocytes from the peripheral blood of mothers giving birth to a child with Down's disease. For control purposes a group of donors of the same age and sex were studied as wells. A decrease of 3H-thymidine incorporation was detected in the lymphocytes of the mothers of such children. The found differences were due to a drop of lymphocyte PH-reactivity in the older maternal age group (over 30 years). Interrelation between the changed function of the maternal immune system and the birth of children with chromosome unbalance are discussed.

Adult↗

Social behavior problems in boys with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a chronic, progressive pediatric disease that affects both muscle and brain. The objectives of the study were to examine parent reported behavior in children with DMD, investigate the influence of chronic illness, intellectual ability and etiology on behavior, and determine whether a specific behavioral profile is associated with DMD. Parental ratings of boys with DMD (n = 181) on the Child Behavior Checklist behavior scales were examined and compared to reported findings of children with other chronic illnesses, unaffected siblings of boys with DMD (n = 86), and children with cerebral palsy (CP) (n = 42). Increased ratings of general behavior problems were reported, and neither physical progression nor intellectual level contributed to behavioral ratings. Among the children with DMD, the Social Problem behavior scale had the greatest number of "clinically significant" ratings (34%). Between-group comparisons showed significantly more boys with DMD were rated as having social behavior problems than either the sibling or CP comparison groups. In addition to the increase in reported behavioral problems likely related to the effects of chronic illness, boys with DMD may be at heightened risk for specific social behavior problems. The specificity of the findings of the behavior profile in DMD may be partially due to the lack of dystrophin isoforms in the central nervous system, and not solely a reactive response to the illness.

Adolescent↗

Foods and additives are common causes of the attention deficit hyperactive disorder in children.

The attention deficit hyperactive disorder (ADHD) is a neurophysiologic problem that is detrimental to children and their parents. Despite previous studies on the role of foods, preservatives and artificial colorings in ADHD this issue remains controversial. This investigation evaluated 26 children who meet the criteria for ADHD. Treatment with a multiple item elimination diet showed 19 children (73%) responded favorably, P < .001. On open challenge, all 19 children reacted to many foods, dyes, and/or preservatives. A double-blind placebo controlled food challenge (DBPCFC) was completed in 16 children. There was a significant improvement on placebo days compared with challenge days (P = .003). Atopic children with ADHD had a significantly higher response rate than the nonatopic group. This study demonstrates a beneficial effect of eliminating reactive foods and artificial colors in children with ADHD. Dietary factors may play a significant role in the etiology of the majority of children with ADHD.

Analysis of Variance↗

Psychophysiological reactivity in female sexual abuse survivors.

This study examined psychophysiological reactivity in 37 female childhood sexual abuse (CSA) survivors. After assessment of posttraumatic stress disorder (PTSD), psychiatric comorbidity, and trauma history, we conducted a psychophysiological assessment of forehead muscle tension, electrodermal activity, and heart rate during a mental arithmetic task and4 script-driven imagery tasks (neutral, consensual sex, pleasant, and trauma). PTSD symptom severity correlated positively with psychophysiologic changes and negative emotions during the trauma imagery task. During mental arithmetic, PTSD symptom severity correlated negatively with autonomic changes and positively with negative emotions. These results extend earlier PTSD research showing trauma-specific increased psychophysiological reactivity related to CSA in women with PTSD. They further suggest a negative association between PTSD severity and autonomic reactions to mental arithmetic.

Adolescent↗

The impact of early adverse experiences on brain systems involved in the pathophysiology of anxiety and affective disorders.

The relative contribution of genetic and environmental factors to the development of the major psychiatric disorders has long been debated. Recently, considerable attention has been given to the observations that adverse experiences early in life predispose individuals to the development of affective and anxiety disorders in adulthood. Corticotropin-releasing factor (CRF) is the central coordinator of the endocrinologic, autonomic, immunologic, and behavioral stress responses. When centrally administered, CRF produces many physiologic and behavioral changes reminiscent of both acute stress and depression. Moreover, CRF has also been implicated in the pathogenesis of a variety of anxiety disorders, mainly through CRF neurocircuits connecting the amygdala and the locus ceruleus. Clinical studies have provided convincing evidence for central CRF hypersecretion in depression, and, to a lesser extent, in some anxiety disorders. Evidence mainly from preclinical studies suggests that stress early in life results in persistent central CRF hyperactivity and increased stress reactivity in adulthood. Thus, genetic disposition coupled with early stress in critical phases of development may result in a phenotype that is neurobiologically vulnerable to stress and may lower an individual's threshold for developing depression and anxiety upon further stress exposure. This pathophysiologic model may provide novel approaches to the prevention and treatment of psychopathology associated with stress early in life.

Anxiety↗

Marked increased risk of Epstein-Barr virus-related complications with the addition of antithymocyte globulin to a nonmyeloablative conditioning prior to unrelated umbilical cord blood transplantation.

Umbilical cord blood (UCB) is increasingly used as an alternative source of hematopoietic stem cells for transplantation for patients who lack a suitable sibling donor. Despite concerns about a possible increased risk of Epstein-Barr virus (EBV) posttransplantation lymphoproliferative disorder (PTLD) after UCB transplantation, early reports documented rates of PTLD comparable to those reported after HLA-matched unrelated marrow myeloablative (MA) transplantations. To further investigate the incidence of EBV PTLD after UCB transplantation and potential risk factors, we evaluated the incidence of EBV-related complications in 335 patients undergoing UCB transplantation with an MA or nonmyeloablative (NMA) preparative regimen. The incidence of EBV-related complications was a 4.5% overall, 3.3% for MA transplantations, and 7% for NMA transplantations. However, the incidence of EBV-related complications was significantly higher in a subset of patients treated with an NMA preparative regimen that included antithymocyte globulin (ATG) versus those that did not (21% vs 2%; P < .01). Nine of 11 patients who developed EBV PTLD were treated with rituximab (anti-CD20 antibody), with the 5 responders being alive and disease free at a median of 26 months. Use of ATG in recipients of an NMA preparative regimen warrants close monitoring for evidence of EBV reactivation and potentially preemptive therapy with rituximab.

Adolescent↗

Pure versus co-occurring externalizing and internalizing symptoms in children: the potential role of socio-developmental milestones.

Co-occurring internalizing and externalizing disorders are moderately prevalent in children, adolescents, and adults (Anderson, Williams, McGee, & Silva, 1987; McConaughy & Skiba, 1994), but much remains to be understood regarding why some children show "pure" versus co-occurring internalizing and externalizing symptoms. One possible influence that has previously not been considered is the failure to attain socio-developmental milestones, which paradoxically may prevent the development of co-occurring symptoms for some children. The present study proposes a model in which failure to attain relevant socio-developmental milestones might explain why some children may not develop heterotypic co-occurring symptoms. Specifically, it is proposed that specific clusters of internalizing symptoms (i.e., high social anxiety, withdrawal, and inhibition) and externalizing symptoms (i.e., high impulsivity, hyperactivity, and emotional reactivity) may be associated with the failure to attain socio-developmental milestones (i.e., poor peer relations for anxious children, lack of self-reflection and evaluation for impulsive/reactive children) that, in turn, may prevent subgroups of children from developing co-occurring, heterotypic symptoms.

Child↗