Gender Nonconformity, Childhood Rejection, and Adult Attachment: A Study of Gay Men

Several childhood factors are reported to be associated with a homosexual orientation in men, including gender nonconformity and rejection by parents and peers. The purpose of this study was to explore the associations between these childhood factors and attachment anxiety (the tendency to experience anxiety regarding potential loss and rejection in close relationships) and attachment avoidance (the tendency to avoid versus seek out closeness in relationships) in gay and bisexual men. A community sample of 191 gay and bisexual men completed questionnaires and an attachment interview. Gender nonconformity was significantly associated with paternal, maternal, and peer rejection in childhood. In addition, paternal and peer rejection, but not maternal rejection, independently predicted attachment anxiety. Peer rejection and, to a lesser extent, paternal rejection mediated the association between gender nonconformity and attachment anxiety. Finally, peer rejection mediated the association between paternal rejection and attachment avoidance. Findings highlight the role of gender nonconformity in contributing to childhood rejection and the importance of peer relationships in the socialization of gay men.     

Human papillomavirus infection in adolescents: a rational approach

Human papillomavirus (HPV) infection has variable clinical manifestations, from transient subclinical disease to serious cervical cancer precursors. An understanding of the natural history of this common sexually transmitted infection is necessary to allow diagnosis of clinically significant disease and judicious application of treatment modalities, especially in young adolescents. This article reviews new recommendations for initiation of screening, revisions in cytology terminology, and evidence-based guidelines for management of lower genital tract disease, including the application of HPV testing.     

Histologic correlates of viral and bacterial infection of the placenta associated with severe morbidity and mortality in the newborn

The purpose of this study was to correlate the histologic features of the placenta with the in situ detection of viral or bacterial nucleic acids in cases of severe morbidity and mortality in the neonatal period. The criteria for the cases were either fetal or neonatal death (11 cases with autopsy material available in 8 cases) or idiopathic severe respiratory distress or central nervous system-related symptoms at birth (49 cases). Controls included 11 placentas from births with no morbidity and 6 placentas that were associated with severe neonatal morbidity of known etiology (trisomy, ruptured uterus, prolapsed cord). The 77 placental tissues were analyzed with a consensus bacterial probe and for a wide variety of viral infections. An infectious cause was found in 46/60 (76%) of cases; these were distributed as follows: enterovirus, 23 cases (22 were coxsackie virus); bacterial (consensus probe), 15 cases; cytomegalovirus (CMV), 4 cases; herpes simplex virus (HSV), 2 cases; parvovirus, 2 cases. The infectious agents localized primarily to Hofbauer cells and trophoblasts. In each of the 8 cases for which autopsy material was available, the same infectious agent that was detected in the placenta was also detected in the autopsy material (spleen, heart, central nervous system, or lungs). No infectious agent was detected in any of the 17 controls. Viral inclusions (only evident for DNA viruses) and stem vessel vasculitis were the 2 histologic findings that were associated with infectious disease in the placenta (P = 0.025). These data show that infection of the villi is highly associated with neonatal morbidity and mortality and that the histologic findings are, in most cases, nonspecific for infection.     

Orally active acaricidal peptide toxins from spider venom

Numerous species of ticks and mites (collectively known as acarines) are serious pests of animals, humans, and crops. There are few commercially available acaricides and major classes of these chemicals continue to be lost from the marketplace due to resistance development or deregistration by regulatory agencies. There is consequently a pressing need to isolate new and safe acaricidal compounds. In this study, we show that two families of peptide neurotoxins isolated from the venom of the Australian funnel-web spider Hadronyche versuta are lethal to the lone star tick Amblyomma americanum. These toxins, which are specific blockers of arthropod voltage-gated calcium channels, induce a pronounced phenotype characterized by an unusual gait that is rapidly followed by paralysis and death. Remarkably, one of these toxins, the calcium channel blocker ω-atracotoxin-Hv1a, is virtually equipotent whether the toxin is injected or fed to A. americanum.     

Pretreatment blood concentrations of chloroquine in patients with malaria infection: relation to response to treatment

Resistance of Plasmodium falciparum to chloroquine has been reported in many areas in Ghana. Most of these reports, which are from hospital-based studies, indicate RI and RII rather than RIII type of resistance. Since high pretreatment levels of chloroquine have also been measured in patients with malaria infection in Ghana, we hypothesized that the 'added effect' of the pretreatment ingested drug to the full dose given at the hospital may be responsible for the low proportion of RIII type of resistance observed. To ascertain this, pretreatment blood levels of chloroquine were correlated with treatment outcomes in 231 paediatric malaria patients, referred to a major hospital in Ghana. The rate of parasite clearance and prevalence of recrudescence, 14 days post-treatment, were determined for each patient. Results from this study showed no correlation between pretreatment chloroquine levels and day 0 parasitaemia. Two hundred and seven patients (89.6 per cent) had parasites that were sensitive to chloroquine whilst 24 (10.4 per cent) had resistant parasites. Of the latter group 17, six, and one patients had P. falciparum parasites, which were resistant at RI, RII and RIII levels, respectively. Seventy-five per cent of the patients without any detectable pretreatment blood chloroquine had parasites that were sensitive to chloroquine whilst 89.8 per cent, 98 per cent, and 100 per cent with pretreatment blood chloroquine concentration ranges of 0.5--100.5 ng/ml, 100.5--200 ng/ml, and >200 ng/ml, respectively, had chloroquine-sensitive parasites. An inverse relationship was thus observed between pretreatment blood chloroquine concentration and the degree of resistance in this study. We conclude that pre-hospital treatment ingested chloroquine contributes significantly to the resolution of malaria in children in Ghana, in the presence of chloroquine resistance.     

Systemic sarcoidosis presenting as a granulomatous tattoo reaction secondary to interferon-alpha treatment for chronic hepatitis C and review of the literature

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Immune alterations involving heightened T-helper-1 responses have been proposed to play a major role in the pathogenesis of sarcoidosis. Interferon-alpha therapy and hepatitis C infection have been implicated in the development of a variety of autoimmune diseases. However, despite the wide use of IFN-alpha therapy for hepatitis C, only a few cases of sarcoidosis have been reported in this context. We report the case of a 42-year-old white female with hepatitis C, who developed systemic sarcoidosis shortly after therapy with IFN-alpha2b. The disease was heralded by the appearance of a cutaneous sarcoid/ foreign body granulomatous reaction at the site of an old tattoo. The sarcoidosis responded to a short course of oral prednisone therapy. We also reviewed the other reported cases and discussed the possible immunological mechanisms involved.     

ErbB and Nrg: potential molecular targets for vestibular schwannoma pharmacotherapy.

OBJECTIVE: Identify molecular targets for development of tumor-specific pharmacotherapeutics aimed at treating vestibular schwannomas (VSs). Activated epidermal growth factor receptor B (ErbB) 2 and ErbB3 are abundantly expressed in VS. ErbB2 signaling is essential for Schwann cell differentiation, survival, and proliferation. VS arise after loss of functional merlin, a putative tumor suppressor. Merlin internalizes ErbB2 receptors in rodent Schwann cells.Unregulated ErbB signaling may contribute to VS tumorigenesis. STUDY DESIGN: Molecular analyses, retrospective clinical correlation. SETTING: Tertiary referral center. PATIENTS: Thirty-eight specimens from patients operated for sporadic (n=21) and neurofibromatosis (NF) 2-related (n=17) VS. INTERVENTION(S): VS analyses via real-time polymerase chain reaction, immunohistochemistry, and correlation with patient clinical data. MAIN OUTCOME MEASURE(S): ErbB signaling molecule expression, tumor size, age, and NF2 status. RESULTS: VS upregulated epidermal growth factor (EGF) receptor in 68% (62% sporadic and 75% NF2-associated VS) and ErbB2 in 84% (76% sporadic and 94% NF2-related VS). ErbB3 was upregulated in 34%, and ErbB4 is downregulated in NF2-related VS. Of EGF receptor (EGFR) ligands, EGF was upregulated in all NF2-related VS, but none of the sporadic VS (p<0.01), and transforming growth factor alpha and beta-cellulin showed upregulation in 67% of NF2-related VS but not sporadic VS (p=0.02 and p=0.01, respectively). Neuregulin (Nrg) was upregulated in 86% of sporadic VS versus 19% of NF2-related VS (p<0.01). EGFR expression levels correlated directly with VS tumor size and inversely with patient age, whereas Nrg expression correlated directly with age (p=0.0005). EGF expression predicts NF2 status, whereas Nrg predicts non-NF2 status (p<0.01). CONCLUSION: These findings implicate the ErbB pathway in VS growth and as potential molecular targets for VS pharmacotherapy.     

Hepatitis C virus nonstructural proteins are localized in a modified endoplasmic reticulum of cells expressing viral subgenomic replicons

For many years our knowledge on hepatitis C virus (HCV) replication has been based on in vitro experiments or transfection studies. Recently, the first reliable system for studying viral replication in tissue culture cells was developed. Taking advantage of this system, we examined in detail the localization of viral nonstructural (NS) proteins in cells containing functional replication complexes. By fractionation experiments and immunomicroscopy, we observed that all NS proteins were associated with the endoplasmic reticulum (ER) membranes, confirming the hypothesis that the ER is the site of membrane-associated HCV RNA replication. Interestingly, NS3 and NS4A were preferentially localized in endoplasmic reticulum cisternae surrounding mitochondria, suggesting additional subcellular compartment-related functions for these viral proteins. Furthermore, the immunoelectron microscopy revealed the loss of the organization and other morphological alterations of the ER (convoluted cisternae and paracrystalline structures), resembling alterations observed in liver biopsies of HCV-infected individuals and in flavivirus-infected cells.