bluuebunny/crossref_metadata_2025 huggingface dataset:
Mammalian Reservoirs and Epidemiology of Rabies Diagnosed in Human Beings in the United States, 1981‐1998
Authors: KREBS JOHN W. , SMITH JEAN S. , RUPPRECHT CHARLES E. , CHILDS JAMES E.
Published: July 2010

Abstract:Between 1981 and 1998, 37 cases of rabies were diagnosed in human beings in the United States. Information directly linking the cause of infection to animal bite was available for only eight of these cases. Indirect incrimination of the vector by analysis of cDNA sequences obtained by reverse transcriptase polymerase chain reaction of samples indicated that for all cases (12/12) believed to have been acquired in foreign countries, variants of the rabies virus (VRVs) associated with dogs (7/12 involved known bite histories) were the cause of the rabies infections. In contrast, VRVs associated with bats (bat‐associated VRVs or BAVs) were implicated as the cause of 88% (22/25) of infections believed to have been acquired within the United States (1/22 involved known bite histories). Sequence analyses revealed that a single BAV (Ln/Ps), associated with rabid silver‐haired (Lasionycteris noctivagans) and Eastern pipistrelle (Pipistrellus subflavus) bats, was implicated in 73% (16/22) of bat‐associated infections. Silver‐haired bats are predominantly solitary and migratory. Eastern pipistrelle bats may occur individually or in small clusters. Both species are only infrequently submitted for rabies testing. Unrecognized bites and unique properties of the Ln/Ps BAV may explain its association with the majority of rabies infections in human beings in the United States.
Development of a Molecular Probe to Baboon Interleukin‐10 mRNA for in Situ Hybridization during Experimental Schistosomiasis
Authors: CHOU TIEN‐MIN , STICH ROGER W. , MARSALA CHRISTINE , SCOTT MELISSA , BROWN CORRIE C. , RAWLINGS CLARENCE A. , DAMIAN RAYMOND T.
Published: July 2010

Abstract: A nucleic acid probe complementary to baboon interleukin 10 (IL‐10) mRNA was developed for in situ hybridization. Highly conserved IL‐10 protein sequences from several mammals were aligned to design oligonucleotide primers flanking a 270‐bp sequence of the target cDNA. RNA was isolated from stimulated peripheral blood mononuclear cells (PBMC). IL‐10 cDNA was reverse‐transcribed from the total PBMC RNA and amplified with the polymerase chain reaction (PCR). Cloning and sequencing of the PCR product confirmed it to be of baboon IL‐10 origin, with 97.8% identity to human and 100% identity to macaque mRNA sequences. The baboon IL‐10 DNA probe hybridized in Southern blots to a 7.9‐Kbp or 8.6‐Kbp band after digestion of genomic baboon DNA with Bam H1 or Eco R1, respectively. Preliminary results with an antisense riboprobe derived from this sequence showed the presence of IL‐10 mRNA in sections of granulomatous tissues.
Characterization of Attenuated Theileria annulata Vaccines from Spain and the Sudan
Authors: GUBBELS MARC‐JAN , VISERAS JAVIER , HABELA MIGUEL A. , JONGEJAN FRANS
Published: July 2010

Abstract: Theileriosis caused by Theileria annulata can be effectively prevented by vaccination with attenuated, cultured schizonts. Although these attenuated vaccines have been applied for a long time, not much is known about the fate of the vaccie strain in the field. Here, two experimental Spanish vaccine strains originating in Cádiz and Cáceres, and one Sudanese strain are studied to address the development of a carrier status and the infectivity for Hyalomma ticks. Moreover, the heterogeneity of the merozoite surface protein, Tams1, was analyzed in search for an attenuation marker. Using the sensitive reverse line blot (RLB) hybridization, the development of a low level carrier status was demonstrated in the Cáceres and Sudanese line vaccinated calves. Although no signal was detected in the Cádiz line vaccinated calves, seroconversion against the schizont stage was observed, as it was in all other calves. The experimental transmission of T. annulata by Hyalomma ticks to naïve calves was unsuccessful for all cell line inoculated calves. Tams1 heterogeneity indicated a clonal selection of parasites during the process of attenuation, but the Tams1 sequence itself has no connection with the attenuation status. In conclusion, a carrier status develops in attenuated schizont culture vaccinated calves, but is not infective for Hyalomma ticks. Based on these data, the risk for spread of the vaccine strains in the field may be very low.
Integrated Molecular Diagnosis of Theileria and Babesia Species of Cattle in Italy
Authors: SPARAGANO O. , LORIA G. R. , GUBBELS M.‐J. , DE VOS A. P. , CARACAPPA S. , JONGEJAN F.
Published: July 2010

Abstract: A reverse line blot hybridization (RLB) test was developed to specifically identify six Theileria spp. (T. annulata, T. parva, T. mutans, T. velifera, T. taurotragi, and T. buffeli/orientalis) and three Babesia spp. (B. bovis, B. bigemina, and B. divergens). No cross reaction was observed with other livestock pathogens (such as Anaplasma marginale, A. centrale, A. ovis, Cowdria ruminantium, Trypanosoma brucei, T. congolense, and T. vivax). This method was used to test bovine blood samples collected in Sicily in April and November, 1998. Preliminary results indicated that T. annulata and T. buffeli/orientalis were the main species observed in cattle blood. Babesia species represented 1.8% and 23.5% in April and November, respectively.
Role of Grooming in Biological Control of Ticks
Authors: HART BENJAMIN L.
Published: July 2010

Abstract: Although many species of wild bovids live in tick infested environments, tick loads are usually kept to very low levels, primarily by frequent self grooming. Evidence from numerous studies on antelope in Africa strongly support the concept that the delivery of bouts of grooming reflects programmed grooming rather than stimulus driven or reactive grooming. In other words, grooming occurs in response to an endogenous generator that produces grooming bouts at periodic intervals, resulting in removal of ticks before they attach and begin to feed. In the same tick exposure environment, animals that groom most have the fewest ticks. The rate of programmed grooming is modulated by a number of interspecific and intraspecific determinants. Interspecific determinants include adult body size and whether or not the evolutionary habitat is tick dense or tick sparse. Intraspecific determinants include developmental stage of growth, gender (e.g., territorial male vs. female), ectoparasite exposure, and stage of arousal. Some of the intraspecific determinants appear to be mediated by systemic physiological influences suggesting there may be ways to improve grooming activity in weak groomers, such as cattle.
Skin Test and Tick Immune Status in Susceptible and Resistant Cattle in Brazil
Authors: BECHARA G. H. , MORELLI J. , SZABÓ M. P.J.
Published: July 2010

Abstract: A cutaneous hypersensitivity test (CHT) was used to correlate host resistance to ticks and type of reaction elicited to unfed larval extract‐ULE of the cattle tick Boophilus microplus in European and Indian cattle. Twenty calves were separated into four groups of five animals each: naïve or preinfested Indian or European cattle. CHT was induced by intradermal inoculation of 0.1 ml of ULE cattle tick B. microplus (50 μg protein) in the calf ear. Ear thickness was measured using calipers before and 10 min, 1, 2, 6, 18, 24, 48, 72, 96, and 144 h postinoculation (PI). Preinfested European calves showed only an immediate type reaction with maximum response (75% increase in ear thickness) at 10 min PI. On the other hand, preinfested Indian calves presented an immediate response with maximum reaction (70% increase in ear thickness) between 10 min and one hour PI, and a delayed type reaction at 72 h PI (60% increase in ear thickness). These results point out the crucial role of the cellular immune response of cattle in the expression of resistance to cattle tick B. microplus. Skin test might be useful in the ranking of cattle according to the susceptibility/resistance to ticks.
Insecticide Resistance Studies on Blattella germanica (Dictyoptera: Blattellidæ) from Cuba
Authors: PANTOJA CRISTINA DIAZ , PEREZ MIRTHA G. , CALVO ERIC , RODRIGUEZ MARIA M. , BISSET JUAN A.
Published: July 2010

Abstract: We studied the levels of resistance to seven insecticides: malathion, chlorpyrifos, pirimiphos‐methyl, propoxur, cypermethrin, deltamethrin, and lambda‐cyhalothrin in nine strains of Blattella germanica (Linnaeus, 1717) collected from sites in Santiago de Cuba and Havana City. The strains from Santiago de Cuba, generally had high levels of resistance to malathion, cypermethrin, deltamethrin, and lambda‐cyhalothrin, but only low levels of resistance to pirimiphos‐methyl, chlorpyrifos, and propoxur. In the strains from Havana City we found a moderate resistance to the organophosphate insecticides, resistance to the pyrethroids (except for three strains that showed susceptibility to lambda‐cyhalothrin), and susceptibility to the carbamate insecticide (propoxur).
The Mechanism of Action of Cytokines to Control the Release of Hypothalamic and Pituitary Hormones in Infection
Authors: McCANN S. M. , KIMURA M. , KARANTH S. , YU W. H. , MASTRONARDI C. A. , RETTORI V.
Published: July 2010

Abstract: During infection, bacterial and viral products, such as bacterial lipopolysaccharide (LPS), cause the release of cytokines from immune cells. These cytokines can reach the brain by several routes. Furthermore, cytokines, such as interleukin‐1 (IL‐1), are induced in neurons within the brain by systemic injection of LPS. These cytokines determine the pattern of hypothalamic‐pituitary secretion that characterizes infection. IL‐2, by stimulation of cholinergic neurons, activates neural nitric oxide synthase (nNOS). The nitric oxide (NO) released diffuses into corticotropin‐releasing hormone (CRH)‐secreting neurons and releases CRH. IL‐2 also acts in the pituitary to stimulate adrenocorticotropic hormone (ACTH) secretion. On the other hand, IL‐1α blocks the NO‐induced release of luteinizing hormone‐releasing hormone (LHRH) from LHRH neurons, thereby blocking pulsatile LH but not follicle‐stimulating hormone (FSH) release and also inhibiting sex behavior that is induced by LHRH. IL‐1α and granulocyte macrophage colony‐stimulating factor (GMCSF) block the response of the LHRH terminals to NO. The mechanism of action of GMCSF to inhibit LHRH release is as follows. It acts on its receptors on γ‐aminobutyric acid (GABA)ergic neurons to stimulate GABA release. GABA acts on GABAa receptors on the LHRH neuronal terminal to block NOergic stimulation of LHRH release. IL‐1α inhibits growth hormone (GH) release by inhibiting GH‐releasing hormone (GHRH) release, which is mediated by NO, and stimulating somatostatin release, also mediated by NO. IL‐1α‐induced stimulation of PRL release is also mediated by intra‐hypothlamic action of NO, which inhibits release of the PRL‐inhibiting hormone dopamine. The actions of NO are brought about by its combined activation of guanylate cyclase‐liberating cyclic guanosine monophosphate (cGMP) and activation of cyclooxygenase (COX) and lipoxygenase (LOX) with liberation of prostaglandin E2 and leukotrienes, respectively. Thus, NO plays a key role in inducing the changes in release of hypothalamic peptides induced in infection by cytokines. Cytokines, such as IL‐1β, also act in the anterior pituitary gland, at least in part via induction of inducible NOS. The NO produced inhibits release of ACTH. The adipocyte hormone leptin, a member of the cytokine family, has largely opposite actions to those of the proinflammatory cytokines, stimulating the release of FSHRF and LHRH from the hypothalamus and FSH and LH from the pituitary directly by NO.
Neurohormones and Catecholamines as Functional Components of the Bone Marrow Microenvironment
Authors: MAESTRONI GEORGES J.M.
Published: July 2010

Abstract: A variety of cytokines and growth factors exert a finely tuned control on the complex series of proliferative and differentiative events called hematopoiesis. Recent studies have shown that neuroendocrine and neural factors may also regulate hematopoiesis. In particular, besides its important immunoenhancing properties, the pineal neurohormone melatonin can also rescue hematopoiesis from the toxic effect of anti‐cancer drugs via the action of T‐helper cell novel opioid cytokines. In turn, these substances bind κ‐opioid receptors expressed in GM‐CSF‐activated macrophage‐like stromal cells and seem to stimulate IL‐1. Adrenergic agents can also affect hematopoiesis. We demonstrated that pre‐B cells express α1B‐adrenoceptors (α1B‐AR) and that their activation by catecholamines results in suppressed myelopoiesis in vitro or protection in vivo against supralethal doses of carboplatin. Most recently, we found that α1B‐AR gene knockout mice show a deranged hematopoietic recovery after sublethal irradiation. Regeneration of pre‐B cells (the cell type expressing α1B‐AR) and of erythrocytes was much faster in knockout than in wild‐type mice. Most interesting, bone marrow cells can synthesize both melatonin and catecholamines. As far as melatonin is concerned, human and murine bone marrow cells contain and synthesize melatonin at a concentration that is three orders of magnitude higher than that normally found in serum. Catecholamines are also present in substantial amounts and originate both from nerve endings and bone marrow cells. These findings open interesting new perspectives and include hematology among the disciplines that would benefit from the integrative NIM approach.
CXC Chemokine Receptors Expression during Chronic Relapsing Experimental Autoimmune Encephalomyelitis
Authors: GLABINSKI ANDRZEJ R. , O'BRYANT SAGE , SELMAJ KRZYSZTOF , RANSOHOFF RICHARD M.
Published: July 2010

Abstract: Chemokines are small proinflammatory cytokines that possess the ability to stimulate migration of inflammatory cells towards the tissue site of inflammation. Previous reports showed that several chemokines may be involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of autoimmune central nervous system (CNS) inflammation. Inflammatory cells respond to chemotactic chemokine gradient through the chemokine receptors (ChRs). The goal of this study was to analyze expression of ChRs belonging to CXC subfamily during different stages of chronic relapsing EAE. We found significantly increased expression of CXCR2 and CXCR4 in the spinal cord during the first and second disease attacks. The kinetics of this expression in CNS and blood suggests that CXCR2 is expressed by leukocytes migrating from the blood, but CXCR4 is expressed mainly by CNS parenchymal cells. Those results support the interpretation that chemokine‐chemokine receptor interactions may play an important role in the development of CNS autoimmune inflammation.
Not All Peripheral Immune Stimuli That Activate the HPA Axis Induce Proinflammatory Cytokine Gene Expression in the Hypothalamus
Authors: REY ADRIANA DEL , RANDOLF ANKE , PITOSSI FERNANDO , ROGAUSCH HEINER , BESEDOVSKY HUGO O.
Published: July 2010

Abstract: Administration of low doses of lipopolysaccharide (LPS) that do not disrupt the blood‐brain barrier (BBB) results in the expression of interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐alpha (TNFα) in the hypothalamus in parallel to stimulation of the hypothalamus‐pituitary‐adrenal (HPA) axis. This endocrine response is triggered by peripheral cytokines, and we recently obtained evidence that brain‐borne IL‐1 contributes to its maintenance. LPS preferentially stimulates cells of the macrophage lineage and B lymphocytes. The possibility that primarily stimulation of other types of peripheral immune cells also results in the expression of proinflammatory cytokines in the brain and in the activation of the HPA axis was investigated. Our results showed that, in contrast to LPS, administration of the superantigen staphylococcal enterotoxin B (SEB), which stimulates T cells by binding to appropriate Vβ domains of the T‐cell receptor, did not result in induction of IL‐1β, IL‐6, and TNFα expression in the hypothalamus. Furthermore, although IL‐2 transcripts in the spleen were highly increased, expression of this gene was not detected in the brain. However, as with LPS, SEB administration also results in elevated levels of glucocorticoids in blood. Therefore, our data suggest that increased expression of proinflammatory cytokines in the brain is not a necessary step in the stimulation of the HPA axis by SEB.
C‐fos and IL‐2 Gene Expression in Rat Brain Cells and Splenic Lymphocytes after Nonantigenic and Antigenic Stimuli
Authors: KORNEVA E. A. , BARABANOVA S. V. , GOLOVKO O. I. , NOSOV M. A. , NOVIKOVA N. S. , KAZAKOVA T. B.
Published: July 2010

Abstract: Immunostimulatory or immunosuppressive stress models were used: (1) rotation stress (RS) and (2) immobilization (restraint) stress (IS) Intraveneous injection of tetanus toxoid (anatoxin) (TT) was chosen as the antigenic stimulus (500 μg/kg weight), and intravenous injection of saline solution was used as the control. Splenic lymphocytes (CBA mice) or different brain structures (Wistar and Sprague‐Dawley rats) were analyzed. The c‐fos and interleukin‐2 (IL‐2) mRNA expression was measured using a digoxigenin (Dig)‐labeled cDNA probe by spot or in situ hybridization. Rotation stress stimulated IL‐2 mRNA synthesis in lymphocytes in the presence of ConA and rIL‐2 by 40%. IL‐2 mRNA synthesis in lymphoid cells obtained from animals after IS and after IS in combination with the administration in vitro of the cytotoxic drug CsA to the splenic lymphocytes was inhibited (30% and 99%), accordingly, as compared with control rats. Induction of c‐fos mRNA synthesis in rat brain cells was noted 30 minutes after RS in the hypothalamus (lateralis hypothalamic area, LHA), thalamus, corpus collosum, and sensorimotor zone of the brain cortex. IL‐2 mRNA synthesis was shown two hours after RS in the same structures. The increased number of c‐fos mRNA‐positive cells two hours after TT injection was shown in the posterior hypothalamus area (PHA), LHA, dorsomedial nucleus (DMH), ventromedial nucleus (VMH), and anterior hypothalamus area (AHA) as compared to the effect of i.v. saline injection. Moreover, IL‐2 mRNA‐positive cell induction was noted in the PHA, DMH, and VMH. Six hours after TT injection, c‐fos mRNA expression was decreased in the PHA, LHA, and AHA. Activation of c‐fos and IL‐2 mRNA was detected in the paraventricularis nucleus 6 hours after TT i.v. injection. Thus, inhibition or stimulation of IL‐2 gene expression in lymphoid cells depends on the nature of the stressors. RS or antigenic stimuli induce c‐fos and IL‐2 gene expression in definite structures of the brain. The dynamics of this process are time dependent. The partial correlation between c‐fos and IL‐2 mRNA expression in localization in brain structures and time dependence was shown.
Beneficial Autoimmune T Cells and Posttraumatic Neuroprotection
Authors: SCHWARTZ MICHAL
Published: July 2010

Abstract: Injuries of the central nervous system (CNS) lead to an inevitable and irreversible loss of function because of the lack of neurogenesis, poor regeneration, and the spread of degeneration. In most tissues, protection and repair are the function of the immune system. It has long been thought that this does not apply to the CNS, where‐because of its immune‐privileged character‐any immune activity was assumed to be detrimental. We have recently proposed, however, that provided care is taken to avoid the attendant risks, both repair and protection of injured CNS neurons can benefit from immune intervention. In the following I will summarize the data that led to this concept and describe the evidence supporting it.
Involvement of Nuclear Receptors in the Enhanced IL‐2 Production by Melatonin in Jurkat Cells
Authors: GUERRERO JUAN M. , POZO DAVID , GARCÍA‐MAURIÑO SOFÍA , OSUNA C. , MOLINERO P. , CALVO JUAN R.
Published: July 2010

Abstract: This report shows that melatonin enhances IL‐2 production by Jurkat cells via a nuclear receptor‐mediated mechanism. Jurkat cells express nuclear (RZRα, RORα1, and RORα2) and membrane (mt1) melatonin receptors, and melatonin binds to Jurkat nuclei and membranes with the same affinity described for human peripheral blood mononuclear cells (PBMCs). Melatonin enhances IL‐2 production by Jurkat cells activated by either phytohemagglutinin (PHA) or phorbol myristate acetate (PMA). PHA activation of Jurkat cells does not change the profile of melatonin receptor expression; on the contrary, PMA activation negatively regulates the mt1 receptor. In the absence of the membrane receptor, melatonin still activates the IL‐2 production. These results show that the expression of the nuclear melatonin receptor is sufficient for melatonin to activate IL‐2 production by Jurkat cells.
Complex Coping Patterns and Their Role in Adaptation and Neuroimmunomodulation: Theory, Methodology, and Research
Authors: TEMOSHOK LYDIA R.
Published: July 2010

Abstract: This paper describes the evolution of a model of adaptative coping, as well as an example of the converse, a maladaptive coping pattern, type C. It was hypothesized that the more closely a coping process resembles the inverted U‐shaped function that characterizes homeostasis for most biological systems, the more likely it is to be adaptive, and to be associated with more positive health outcomes. Maladaptive learned coping patterns, such as type C coping, represent deviations from homeostasis in that they fail to recognize, respond appropriately to, and/or resolve stressors, thus keeping the physiological stress response chronically engaged, with subsequent long‐term damage to implicated biological systems. This interpretation of how maladaptive coping patterns such as type C can influence health outcomes is consistent with findings from the author's 20‐year program of research on the type C pattern, its assessment, and its association with poorer health indicators and outcomes in cancer (malignant melanoma) and HIV/AIDS.
Cooperation of Pituitary Hormone Prolactin with Interleukin‐2 and Interleukin‐12 on Production of Interferon‐γ by Natural Killer and T Cells
Authors: MATERA LINA , MORI MARCELLA
Published: July 2010

Abstract: The pituitary hormone prolactin (PRL) is also produced by cells of the immune system and participates in early and late T cell activating events. We have previously shown a modulatory role of PRL during maturation of dendritic cells (DC). Production of IL‐12 by T cell receptor (TCR)‐activated DC is necessary for T cells to acquire the Th1 cytokine (i.e., IFN‐γ secreting) profile, which is associated with activation of cellular response. In a separate work, PRL has been shown to increase IFN‐γ synthesis by natural killer (NK) cells. We have extended that study by exploring the ability of PRL to induce IFN‐γ production by T and NK cells in the presence of the specific stimuli IL‐12 and IL‐2. The individual effect of PRL, IL‐12, and IL‐2 was specific for NK cells, and IL‐2 and IL‐12 were much more efficient than PRL. Cooperation of IL‐2 and PRL was observed on NK cells. IL‐2‐induced synthesis of IFN‐γ was increased by physiological concentrations of PRL but was unaffected or inhibited by high concentrations. By contrast, optimal enhancement of IL‐12‐induced IFN‐γ release was observed with T cells but not with NK cells. Unexpectedly, interaction between PRL and IL‐12 occurred only at high concentrations of PRL. These data indicate a complex role of PRL in the cytokine network and point to a revaluation of the proposed immunosuppression by stress‐related hyperprolactinemia.
Growth Hormone and Prolactin Expression in the Immune System
Authors: KOOIJMAN RON , GERLO SARAH , COPPENS ASTRID , HOOGHE‐PETERS ELISABETH L.
Published: July 2010

Abstract: Prolactin (PRL) and growth hormone (GH) are pituitary hormones that play pivotal roles in lactation and body growth, respectively. In addition, both hormones have been implicated as modulators of immune responses. Since the expression of GH and PRL by leukocytes points to auto‐crine or paracrine roles during immune responses, our study is aimed at PRL‐and GH‐production in leukocytes. We show that human peripheral blood granulocytes, which express GH and PRL mRNA, contain high molecular‐weight immunoreactive variants of GH and PRL (37 and 43 kDa, respectively), but not the pituitary‐sized hormones. Secretion of these variants, or biologically active material as assessed by the Nb2 bioassay, was not detected. On the other hand, certain leukemic myeloid cells secrete 23‐kDa, pituitary‐sized, PRL, which is biologically active.
Stress and Chemotherapy: Combined Effects on Tumor Progression and Immunity in Animal Models
Authors: GIRALDI TULLIO , ZORZET SONIA , PERISSIN LAURA , RAPOZZI VALENTINA
Published: July 2010

Abstract: In mice bearing Lewis Lung Carcinoma, rotational and restraint stress specifically increases the formation of lung metastasis, and restraint stress markedly attenuates the antitumor effects of cyclophosphamide. The aim of this investigation was therefore to examine the effects of restraint stress on tumor metastasis in mice bearing MCa mammary carcinoma, and on the effectiveness of CNU and DTIC. Restraint stress increases MCa mammary carcinoma metastasis, caused a marked reduction in cyclophosphamide activity, and a minor attenuation of the effects of CCNU and DTIC. The possible occurence of F seasonal factors, observed for the increase by rotational stress of Lewis lung carcinoma metastasis, was also determined for cyclophosphamide effectiveness. The survival time of control mice is longer in February than in June, and is not appreciably modified by rotational stress. The effects of cyclophosphamide are similar in both seasonal periods, and are similarly attenuated by rotational stress. The seasonal effects of rotational stress, and the reduction of the effects of cyclophosphamide caused by rotational stress, are accompanied by corresponding variations in the number of CD3+ and CD4+ splenic T‐lymphocyte subsets and in the CD4+/CD8+ ratio, respectively. The reported effects of stress on tumor progression and on the effectiveness of cyclophosphamide thus appear to occur via modulation of immune responses of the host directed against the tumor. These data appear of interest for their experimental implications, and suggest the opportunity to consider the role that the stress during treatment may play in determining the effectiveness of clinical antitumor chemotherapy.
SOCS Proteins: Modulators of Neuroimmunoendocrine Functions: Impact on Corticotroph LIF Signaling
Authors: AUERNHAMMER C. J. , BOUSQUET C. , CHESNOKOVA V. , MELMED S.
Published: July 2010

Abstract: Several members of the newly characterized family of suppressor of cytokine signaling (SOCS) proteins‐such as SOCS‐1, SOCS‐3, and CIS‐act as negative regulators of the cytokine‐induced Jak‐STAT signaling cascade. The expression of SOCS proteins is stimulated by a variety of cytokines and hormones in a tissue‐specific manner. This article reviews our current understanding of SOCS proteins and their role as modulators of neuroimmunoendocrine functions, for example, in signaling of leptin, growth hormone, and prolactin, specially focusing on the impact of SOCS proteins on corticotroph leukemia inhibitory factor (LIF) signaling. LIF, a member of the gp130 sharing cytokine family, modulates pituitary development, POMC gene expression, and ACTH secretion. Current data on the negative autoregulatory function of the suppressor of cytokine signaling, SOCS‐3, in LIF‐induced POMC gene expression and ACTH secretion are extensively discussed.
Expression of Preproenkephalin mRNA and Production and Secretion of Enkephalins by Human Thymocytes
Authors: KAVELAARS ANNEMIEKE , HEIJNEN COBI J.
Published: July 2010

Abstract: Human thymocytes were tested for the capacity to express the pre‐proenkephalin (PPE) gene and for production of the end product met‐enkephalin (MENK). It is shown here for the first time that the cytokines IL‐2, IL‐4, IL‐6, AND TGF‐β are capable of inducing PPE mRNA expression. Moreover, a culture of thymocytes with the cytokines results in intracellular expression of MENK as determined by immunohistochemistry. Thymocytes do not secrete detectable amounts of MENK, however, but only the larger MENK‐containing peptides or proteins. Cytokines IL‐1β and IL‐10 increase the expression of PPE mRNA in 50% of the thymuses tested, whereas IFN‐γ does not induce changes in PPE mRNA expression.
Androstenetriol and Androstenediol: Protection Against Lethal Radiation and Restoration of Immunity After Radiation Injury
Authors: LORIA R. M. , CONRAD D. H. , HUFF T. , CARTER H. , BEN‐NATHAN D.
Published: July 2010

Abstract: Androstenetriol (AET) and Androstenediol (AED) upregulate host immunity, leading to increased resistance against infections. AET augments IL‐2, IL‐3, IFNγ levels, and counteracts hydrocortisone immune suppression. AET and AED at a dose of 0.75 mg/‐ and 8.0 mg/25‐g mouse, protected 60 and 70%, respectively, of C57/BL/6J mice irradiated with a lethal dose. These hormones also protected mice irradiated with 6 Gy and infected with a coxsackievirus B4 LD50. AET significantly increased spleen lymphocyte numbers at 7, 14, and 21 days after a 6‐Gy exposure. Fluorescent activated cell‐sorter analysis of irradiated mice, spleen, and bone marrow showed that AET significantly augmented the myeloid precursor markers, CD11b/Mac‐1, and B220 (pan B), as well as the absolute numbers of CD4+/CD8+ cells over the 21 days of testing. Overall, the data are consistent with AET/AED inducing a more rapid recovery of all hematopoietic precursors from the small number of surviving stem cells.
The Role of Oxidative Stress in Viral Infections
Authors: BECK M. A. , HANDY J. , LEVANDER O. A.
Published: July 2010

Abstract: Oxidative stress is implicated as a pathogenic factor in a number of viral infections. Our work has shown that nutritionally induced oxidative stress exacerbates the pathogenesis of coxsackievirus B3 (CVB3) infection in mice. Of particular note, mice fed on a diet deficient in antioxidants developed myocarditis when infected with a normally benign strain of CVB3. This change in virulence was found to be due to changes in the viral genome. Immune functions of the oxidatively stressed mice were also altered. Another example of the effect of oxidative stress on a viral pathogen took place in Cuba in the 1990s. An epidemic of optic and peripheral neuropathy in the population occurred that was associated with a lack of dietary antioxidants and with smoking (a pro‐oxidant). A coxsackie‐like virus was isolated from the cerebrospinal fluid from 84% of patients cultured. Thus, oxidative stress can have profound effects, not only on the host, but on the pathogen as well.
Fat Redistribution in HIV‐Infected Patients: A New Hormonal‐Immune Disorder?
Authors: NORBIATO GUIDO , TRIFIRÒ GIULIANA , GALLI MASSIMO , GERVASONI CRISTINA , CLERICI MARIO
Published: July 2010

Abstract: Multidrug antiretroviral regimes in HIV‐infected patients may have side effects. The most frequent side effects are changes in fat metabolism and distribution. We describe a particular pattern of fat redistribution (FR), characterized by a progressive enlargement of breast and abdominal girth and fat loss in the lower limbs, which occurs in approximately 10% of HIV‐infected women treated with combined antiretroviral therapy. To elucidate the metabolic, endocrine, and immunologic consequences of the observed disturbance, we measured serum lipids, glucose, C‐peptide, ACTH, plasma, urinary cortisol, and cytokines IL‐2, IFNγ, Il‐4, IL‐10, Il‐12, and TNFα in 36 patients with FR and in a control group without FR. There were no significant differences in hormonal and metabolic laboratory testing between the two groups. Immunology studies showed that in vitro production of TNFα and IL‐10 was lower and IL‐12 production higher in SR patients. Whether or not such immune alterations may be reponsible or be caused by fat redistribution remains to be explained. One year after the follow up, 50% of the patients treated with triple therapy developed lipodystrophy, characterized by weight loss, face‐wasting, and hyperglycemia; the remaining 50% remained unchanged. In 13 patients the 3TC withdrawal was followed by improvements of the syndrome in 50% and of lipodystrophy in about 25%. These data suggest that the FR syndrome is frequent in patients treated with 3TC and that it is associated with characteristic changes in the cytokine production.
Immunoendocrinologic Abnormalities in Human Immunodeficiency Virus Infection
Authors: CLERICI MARIO , GALLI MASSIMO , BOSIS SIMONA , GERVASONI CRISTINA , MORONI MAURO , NORBIATO GUIDO
Published: July 2010

Abstract: Alterations in the production of adrenal steroids and a complex pattern of dysregulation in cytokine profiles accompany the progression of HIV infection. Cortisol levels increase in HIV infection, while those of dehydroepiandrosterone (DHEA), a physiologic antagonist of the immunoregulatory activities of cortisol, decrease. A shift from type‐1 to type‐2 cytokine production is also detected in most patients during disease progression. This shift is summarized as a defective production of interferon gamma (IFNγ), interleukin‐2 (IL), and IL‐12 accompained by increased production of IL‐4, IL‐5, IL‐6, and IL‐10. IFNγ and IL‐2 are suppressed, while the generation of IL‐4 is stimulated by cortisol and pharmacological doses of glucocorticoids (GC). GC and IL‐4 stimulate the differentiation of B lymphocytes into IgE‐producing plasma cells, the concentration of which augments in HIV infection. Finally, GC induces programmed cell death (PCD) in a variety of different cells, including mature T lymphocytes. Because (1) TH1 but not TH2 undergo rapid Fas‐mediated PCD upon antigen‐stimulation, and (2) TH2 clones preferentially survive in vitro cell cultures, the progressive shift from type‐1 to type‐2 cytokine production observed in HIV infection could be at least partially provoked by the increase in the production of cortisol and the reduction of DHEA. Progression of HIV infection to AIDS can be controlled by highly active antiretroviral therapy (HAART); HAART drastically reduces HIV plasma viremia, but is less effective in immune reconstitution. Additionally HAART is associated in a sizable portion of patients by complex lypodistropyc phenomena that often involve the endocrine system.
7α‐Hydroxy‐Dehydroepiandrosterone and Immune Response
Authors: MORFIN R. , LAFAYE P. , COTILLON A. C. , NATO F. , CHMIELEWSKI V. , POMPON D.
Published: July 2010

Abstract: In human and murine lymphoid organs, circulating 3β‐hydroxysteroids, including pregnenolone (PREG), dehydroepiandrosterone (DHEA), and epiandrosterone (EPIA), are 7α‐hydroxylated by a cytochrome P450 identified in the hippocampus as P4507B1. Mouse and human lymphoid organs produced different patterns of 3β‐hydroxysteroid 7α‐hydroxylation with the absence of pregnenolone and epiandrosterone hydroxylation in human and mouse, respectively. Both 7α‐hydroxy‐DHEA and 7α‐hydroxy‐EPIA triggered a significant increase of antitetanus toxoid and anti‐Bordetella pertussis toxins IgGs production in cultures of activated B + T cells derived from human tonsils, whereas both 7α‐hydroxy‐PREG and 7α‐hydroxy‐DHEA increased the immune response in mouse. Paracrine action of 7α‐hydroxysteroids resulted from their production in cells of the lymphoid organs. Comparison of P4507B1 sequences in rat, human, and two mouse species showed that one amino acid change might explain important differences in KM for 7α‐hydroxylation, and suggested that such differences might contribute to the extent of immune response.
Global Strategies for the Prevention of HIV Transmission from Mothers to Infants
Authors: KARIM QUARRAISHA ABDOOL
Published: July 2010

Abstract: The first part of this paper provides a brief overview of the global situation, the second will describe several scenarios that capture the key features of the emerging epidemics, and the third will present the specific challenges that these scenarios pose to us in terms of preventing the further spread of HIV.
Access to Voluntary Counseling and Testing for HIV in Developing Countries
Authors: COOVADIA HOOSEN M.
Published: July 2010

Abstract: The counseling that precedes and follows testing of subjects for HIV has become, quite unexpectedly, a focal point for assessment of the ethical propriety, availability, and appropriateness of health services during the AIDS epidemic. It can be anticipated that in the worst affected regions, Voluntary Confidential Counseling and Testing (VCCT) will be an integral component of “…access to comprehensive, essential, quality health care” which is WHO's goal of “Health for All” in the next century. The role, purpose, location, and methods of VCCT, which were reviewed at the previous Global Strategies Conference in 1997, are summarized. Currently understood objectives of VCCT include acceptance of the test, provision of care for HIV‐infected individuals (particularly pregnant women), prevention of HIV transmission, and psychosocial support. Many countries in Africa are gradually instituting VCCT as part of their Primary Health Care package. For example “…access to care, counselling and support” for HIV/AIDS and STDs is one of the top 10 national priorities in South Africa. However, closer examination in the country reveals personnel and skill shortages, inability of half the primary health care (PHC) clinics to provide antenatal services, and HIV testing being offered in only 56%. Condom availability is generally good, but termination of pregnancy is undertaken in a bare 27% of hospitals. In other regions of Africa, VCCT is also deficient in many respects: medical services are often unavailable, support is absent, availability is restricted and there are few trained counselors. Consequently, workloads are heavy. Requirements for effective counseling will be listed. The global determinants of inequities in accessing VCCT, such as the GNP and the crushing debt burden borne by poor countries, are discussed. A third of women worldwide receive no antenatal care, and just 60% of the roughly 133 million annual births throughout the world are attended by trained health personnel. Even when VCCT services are available, they are often not acceptable. The overwhelming majority of African women appear to accept HIV testing, but only a proportion (59‐61% in recent intervention trials) return for the results. Obstacles to be overcome for provision of VCCT services are identified. Evidence for a positive impact of VCCT services includes facilitated decision‐making, acceptance and coping with HIV, improved family and community acceptance, increased condom use, and reduced gonorrhea rates and HIV transmission.
Breast Milk Transmission of HIV‐1 Laboratory and Clinical Studies
Authors: VAN DE PERRE PHILIPPE
Published: July 2010

Abstract: Breast milk transmission of HIV‐1 can occur at any time during the entire duration of breastfeeding. The risk of late postnatal transmission (after 2.5 months of age) is 3.2 per 100 child/years of breastfeeding, but early postnatal transmission may be more frequent than previously thought. Exclusive breastfeeding has been suggested to be less risky than mixed feeding. Breast milk contains immunoactive cells, antiinfectious substances, immune globulins, cytokines, and complement factors. HIV‐1 has been found in breast milk from HIV‐infected mothers as both cell‐associated and cell‐free particles. Mastitis has been suggested to facilitate transmission of HIV‐1. The portal of entry of HIV‐1 in the infant mucosae may involve tonsilar lymphoepithelium, M cells, and enterocytes from intestinal surfaces. Anti‐HIV‐1 SIgA and IgM in breast milk and intestinal fluid may confer some protection. Transmission of HIV‐1 by breastfeeding has to be taken into account in designing interventions to reduce/prevent mother‐to‐child transmission in developing countries.
Psychosocial and Community Perspectives on Alternatives to Breastfeeding
Authors: BASSETT MARY T.
Published: July 2010

Abstract: In developing countries, what advice to give HIV‐positive mothers on infant feeding options remains a vexing public health issue. This paper reviews data on infant feeding practices in sub‐Saharan Africa, the cultural context of breastfeeding, and the still meager literature of decision‐making by HIV‐positive mothers, following impartial counseling. Although prolonged breastfeeding is common, weaning foods typically are introduced early. A minority of women practice the recommended exclusive breastfeeding for 4‐6 months. Breastfeeding taboos, expecially regarding colostrum, are common. The usual reason for introduction of weaning foods is to ensure that the baby has enough food. Exclusive formula feeding is perceived as stigmatizing, but acceptable with husband support. The main perceived barrier to formula is cost. Health workers may be less effective in conveying the risk of formula compared to the risk of HIV transmission in breast milk. Studies presently available regarding these issues are few and involve small samples. More studies are planned, and some are under way. By offering actual feeding choices to HIV‐positive women, observing what choices they make, and monitoring the outcomes of these choices, we will be better placed to give advice.
Lack of Evidence of Mitochondrial Dysfunction in the Offspring of HIV‐Infected Women: Retrospective Review of Perinatal Exposure to Antiretroviral Drugs in the Perinatal AIDS Collaborative Transmission Study
Authors: BULTERYS MARC , NESHEIM STEVEN , ABRAMS ELAINE J. , PALUMBO PAUL , FARLEY JOHN , LAMPE MARGARET , FOWLER MARY GLENN ,   THE PERINATAL SAFETY REVIEW WORKING GROUP
Published: July 2010

Abstract: A recent report suggesting mitochondrial dysfunction among eight HIV‐exposed but uninfected children exposed perinatally to nucleoside reverse transcriptase inhibitors (NRTIs) prompted a review within the Perinatal AIDS Collaborative Transmission Study (PACTS). A standardized retrospective review was conducted of 118 deaths at <5 years. Deaths were classified as unrelated to mitochondrial dysfunction (Class 1), unlikely related (Class 2), possibly related (Class 3), or likely related or proven (Class 4). Among 35 deaths recorded in HIV‐uninfected or indeterminate children, none were classified in either Class 2, 3, or 4. We also reviewed signs or symptoms consistent with possible mitochondrial dysfunction among 1,954 living uninfected children. Only one child was in Class 3 and two siblings were in Class 2; none had perinatal antiretroviral drug exposure. We found no evidence indicating that uninfected infants exposed to perinatal NRTIs died of mitochondrial disorders or that living exposed children had symptoms of mitochondrial dysfunction.
Factors Impacting on Drug Choices: Issues for Developing Countries
Authors: SPECTOR STEPHEN A
Published: July 2010

Abstract: In considering factors that impact on drug choices for children in developing countries, it is important to learn from the advances in antiretroviral therapy that have been made in the United States and other developed countries. Abundant clinical data indicate that monotherapy with antiretroviral agents, no matter how potent, is inadequate and that children should be treated with three or more drugs. When treatment regimens are changed, at least two new drugs should be started simultaneouly to avoid the rapid development of resistance. Understanding the impact of host and viral genotypes may provide information as to how best to treat the individual child. However, at present, I believe that with limited resources, the best use of antiretrovirals for children is in disease prevention. Thus, antiretrovirals to prevent mother‐to‐infant transmission should be given the highest priority. Second, children in the first year of life are at highest risk of progression and should be treated with trimethoprim‐sulfamethoxazole to prevent Pneumocystis carinii pneumonia, and targeted for receiving antiretrovirals. Moreover, treating children without an overall plan is unacceptable. Treatment with drugs because they are available will have little impact on the quality of life or disease progression unless they are used in combination. There should be no reason for children, no matter where they might live, to receive suboptimal antiretroviral therapy. For this reason, I call upon industrialized countries and the World Bank to help provide resources for the care and treatment of HIV‐infected children. Additionally, I would propose that pharmaceutical companies provide support for the care and treatment of HIV‐infected children. The drugs and financial support provided by pharmaceutical companies should go to a central foundation or group that will optimize the use of these resources for children in developing countries. I would also propose that in the United States, Europe, and other industrialized countries the patents on antiretroviral drugs be extended according to a formula based on the donation of a pharmaceutical company. It is only through a unified effort that we will be able to adequately treat all children infected with HIV regardless of where they might live.
The Uteroglobin Fold
Authors: CALLEBAUT ISABELLE , POUPON ANNE , BALLY RÉNÉE , DEMARET JEAN‐PHILIPPE , HOUSSET DOMINIQUE , DELETTRÉ JEAN , HOSSENLOPP PAUL , MORNON JEAN‐PAUL
Published: July 2010

Abstract: Uteroglobin (UTG) forms a fascinating homodimeric structure that binds small‐ to medium‐sized ligands through an internal hydrophobic cavity, located at the interface between the two monomers. Previous studies have shown that UTG fold is not limited to the UTG/CC10 family, whose sequence/structure relationships are highlighted here, but can be extended to the cap domain of Xanthobacter autotrophicus haloalkane dehalogenase. We show here that UTG fold is adopted by several other cap domains within the α/β hydrolase family, making it a well‐suited “geode” structure allowing it to sequester various hydrophobic molecules. Additionally, some data about a new crystal form of oxidized rabbit UTG are presented, completing previous structural studies, as well as results from molecular dynamics, suggesting an alternative way for the ligand to reach the internal cavity.
Physiological Regulation of Uteroglobin/CCSP Expression
Authors: CHANG ALBERT , RAMSAY PATRICIA , ZHAO BIHONG , PARK MOON , MAGDALENO SUSAN , REARDON MICHAEL J. , WELTY STEPHEN , DEMAYO FRANCESCO J.
Published: July 2010

Abstract: Uteroglobin/CCSP is expressed specifically in the Clara cells. This allows the gene to be used as a marker to identify the elements regulating the physiologic and cell‐specific expression of this gene. The regulation of UG/CCSP by IFN‐γ was shown to be at the level of the proximal promoter by the upregulation of HNF3β. This has allowed the determination of the factors responsible for the expression of UG/CCSP.