Improved design of proton source and low energy beam transport line for European Spallation Source.

The design update of the European Spallation Source (ESS) accelerator is almost complete and the construction of the prototype of the microwave discharge ion source able to provide a proton beam current larger than 70 mA to the 3.6 MeV Radio Frequency Quadrupole (RFQ) started. The source named PS-ESS (Proton Source for ESS) was designed with a flexible magnetic system and an extraction system able to merge conservative solutions with significant advances. The ESS injector has taken advantage of recent theoretical updates and new plasma diagnostics tools developed at INFN-LNS (Laboratori Nazionali del Sud, Istituto Nazionale di Fisica Nucleare). The design strategy considers the PS-ESS and the low energy beam transport line as a whole, where the proton beam behaves like an almost neutralized non-thermalized plasma. Innovative solutions have been used as hereinafter described. Thermo-mechanical optimization has been performed to withstand the chopped beam and the misaligned focused beam over the RFQ input collimator; the results are reported here.

Mother-to-infant transmission of hepatitis C virus.

Anti-hepatitis C virus (HCV) antibodies and HCV-RNA were measured in the sera of 22 anti-HCV positive, HIV-1 negative mothers and their infants. ELISA and RIBA II were used for anti-HCV determination. HCV-RNA was measured by a nested polymerase chain reaction. HCV-RNA was found in 12 of 22 mothers. All 22 children were followed for 12 months. All were anti-HCV positive by the fourth month; 18 became anti-HCV negative between the 8th and 12th month. HCV-RNA was detected in 5 of 22 infants in the fourth month. They remained HCV-RNA positive. All children born to HCV-RNA negative mothers were HCV-RNA negative while 5 of 12 babies born to HCV-RNA positive mothers were infected. All five infected babies were born to mothers infected through transfusions or drug use. ALT levels in mothers seemed to have no effect on mother-to-infant transmission. Hence evidence for perinatal transmission of HCV from HCV-RNA positive mothers was demonstrated in the present study.

Pathogenesis of posttransfusion viral hepatitis in children with beta-thalassemia.

The pathogenesis of posttransfusion hepatitis was determined in 14 children with beta-thalassemia. All had blood samples obtained in 1980 or 1981, were vaccinated against hepatitis B virus in 1983 and had another serum sample collected in 1989. Seven children had detectable antibodies against hepatitis C virus before vaccination, and all were positive in 1989. With specific solid-phase enzyme immunoassays, all children had antibodies against hepatitis B virus, X and polymerase antigens in 1981, and six had one or both antibodies in 1989. Hepatitis B virus infection was confirmed by means of polymerase chain reaction, which demonstrated virus DNA in 13 of the 14 children. The amplification products spanning the X/precore region were smaller than expected, suggesting mutations in this region. Cloning and sequencing of these products revealed deletions spanning part or all of the X gene. The results show that these children were infected with hepatitis B virus even without other markers in serum, that hepatitis B persists years after vaccination and that such infections are associated with the presence of X deletion mutants. Coinfection with hepatitis B and C viruses, the former containing a new class of variants, is common in children with beta-thalassemia.

Fish allergy in children.

Fish allergy is a relevant clinical problem in fish eating and/or processing communities but, because of the technologic advances of the preserved food industry, it may now be said to be a worldwide problem. Among 558 consecutive children referred for atopic diseases, 25 (4.48%) subjects skin test- and RAST- positive to cod were recorded and we extrapolated that about 4-5/1000 children have allergy to cod in our areas. As a group, children with cod allergy seem to manifest a higher atopic condition and more severe clinical manifestations. IgE level z-score (mean +/- SD) was significantly (P < .001) higher in 68 cod-positive children (14.27 +/- 3.87) than in 533 children positive to other inhalant and/or food allergens (8.12 +/- 4.06). In spite of a smaller median age (59 months), cod-positive children had a higher frequency of asthma (41/68 = 60.2%) than children with other allergies, and age at the onset of asthma was significantly (P < .001) younger in the former (32 months) than in the latter (41 months) subjects. In addition, urticaria-angioedema was more frequently recorded in cod-allergic children (23/68 = 33.8%) than in patients with allergy to inhalants (26/410 = 6.3%; P < .01), inhalants and foods different from cod (11/74 = 14.8%; P < .01), or foods different from cod (6/49 = 12.2%; P < .01). The male:female ratio in cod-allergic children (3.53) was significantly higher than that observed in children with allergy to inhalants (1.78; P = .037) or foods (0.68; P < .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Reduced natural killer function in children with recurrent respiratory tract infections]. / Ridotta funzionalità natural killer in bambini con infezioni respiratorie ricorrenti.

Respiratory infections are the major cause of disease in childhood in the industrialized areas of the world. This essentially depends on two factors: immunological immaturity and immunological naivety. In most cases a virus has been considered the causative agent in respiratory infection. A defect in immune responses has been described in children with recurrent respiratory infections and in particular a decrease in CD4/CD8 T lymphocyte ratio or in IL-2 and IFN-gamma production. Our results show that Natural Killer (NK) cell activity is defective in children with recurrent respiratory infections. That is particularly noteworthy since NK cells play an important role in host defense against viral infections. At present it is difficult to understand whether the NK defect is a primary defect or it is secondary to viral infections. Further studies will help to clarify whether NK decreased activity depends on a cell damage directly caused by virus or it depends on the decreased levels of cytokines.

[Hepatitis B virus: new markers and their immunology]. / Il virus dell'epatite B: i nuovi markers e la loro immunologia.

Hepatitis B virus (HBV) is one of the most important causes of chronic liver disease. HBV is a DNA virus with an external glycoprotein surface and an internal nucleocapsid which contains the viral genome. HBV infection is revealed by the appearance of specific markers. Some of these markers are well known and their presence in serum is important to understand the behaviour of the disease. Among them HBsAg, HBeAg, anti-HBs and anti-HBe are found in serum, so as anti-Core; the HBcAg may be found in hepatic tissue and marks infectivity and virus replication. In the few last years some new antigens and antibodies have been studied and their importance in diagnosis and follow-up of hepatitis has been recognized. HBxAg, Pre-S and DNA-Polymerase (Pol) seem to be specific and early signals of viral replication. More studies showed the trans-activating properties of HBxAg; actually the X protein seems to be involved in replicative cycle of HBV. Many Authors also demonstrated a relationship between the presence of X in serum and/or liver and the progression of disease to cirrhosis and hepatocellular carcinoma. The Pol antigen and its antibody seem to be very common markers of HBV infection in serum of patients with hepatitis. Moreover their presence is the only signal of viral infection in some patients which have no other marker of HBV. More studies are of course needed to exactly establish the significance of these new markers and their importance for diagnosis and prognosis of HBV infection.

Characteristics of woodchuck hepatitis X-antigen in the livers and sera from infected animals.

This study tests the hypothesis that woodchuck hepatitis virus encoded X-antigen expression correlates with viral replication, with hepatitis, or with both. Paired liver and serum samples from each of 55 infected woodchucks were used. Seven of 8 carriers with high levels of viral DNA in serum also had X-antigen in serum. In contrast, the frequency of X-antigen in serum was low among infected woodchucks that did not have viral surface antigen in the serum. Statistical analysis showed a significant relationship between X-antigen in serum and markers of viral replication. Woodchuck hepatitis X-antigen (WHxAg) expression in liver but not serum of carriers closely correlated with the presence of hepatitis. The finding of X-antigen in the liver of infected animals with hepatitis that cleared the virus surface antigen from serum also suggests that X-antigen is associated with ongoing hepatitis. Hence, the persistence of WHxAg in serum may signal continuing viral replication and, in liver, may contribute to the pathogenesis of chronic infection.

[Changed levels of substance P and somatostatin in HIV-positive children]. / Alterati livelli di sostanza P e somatostatina nei bambini HIV positivi.

Substance P (sP) and Somatostatin (SOM), so as other neuropeptides can modulate neurologic and immunologic functions. sP has been described to enhance both in vitro and in vivo immunoglobulin synthesis. On the contrary, SOM has an inhibitory effect on the same activity. The modulating effect is more evident on IgA isotype. Hypergammaglobulinemia and in particular high levels of IgA is a common finding in pediatric AIDS and an imbalance among regulatory effects of neuropeptides might be suggested. In order to evaluate the plasma levels of sP in pediatric AIDS we studied 15 children with HIV infection (status P2), 10 seronegative children born to HIV positive mothers and 10 healthy children of the same age. All the HIV positive children had high plasma levels of IgG and IgA. The plasma level of sP was extremely higher in HIV positive children while no significant difference was found between seronegative children born to HIV positive mothers and healthy children. SOM was decreased in HIV positive children when compared to control groups but a significant difference was not reached. It might be supposed that HIV infection, through a dysregulation among neuropeptides interferes on immune functions and in particular on IgA synthesis. On the other hand it might be suggested that the imbalance between sP and SOM depends on the viral infection of immune cells since it has been demonstrated that SOM and other neuropeptide are synthesized by lymphoid tissue. Further studied relevance of neuropeptide disorders in pediatric AIDS.

Hepatitis B x antigen and polymerase antibodies in the serum of hepatitis B carriers with or without hepatitis delta virus infection. Effects of interferon treatment.

Previous work has shown that the hepatitis B x antigen (HBxAg) and antibodies directed against the polymerase of hepatitis B virus (anti-pol) are early markers of hepatitis B virus (HBV) replication in natural infections. The present study was carried out to test the hypothesis that the appearance of one or both of these markers signaled reactivation in chronic carriers with liver disease who were treated with alpha-interferon (IFN). The results show that HBV DNA decreased among the patients who responded to therapy, and that among these responders, neither HBxAg nor anti-pol became detectable in serum for 12 months after treatment, in contrast to controls. Hence, the loss of HBxAg and anti-pol correlate with decreased levels of HBV DNA in response to IFN therapy. However, different patterns of HBxAg and anti-pol were observed among alpha-IFN-treated HBV carrier patients who were also chronically infected with the hepatitis delta virus (HDV). The treatment of such patients often resulted in the loss of HDV RNA from serum and delta antigen from liver. Most of these patients had increased levels of HBV DNA in serum. HBxAg and/or anti-pol also became detectable in patients who lost markers of HDV, implying that the suppression of HDV by IFN is accompanied by the appearance of early markers of HBV reactivation in some of the treated patients.

HBxAg in the liver from carrier patients with chronic hepatitis and cirrhosis.

Formalin-fixed, paraffin-embedded specimens from 110 cases of chronic hepatitis and 108 cases of cirrhosis were stained for HBxAg by the avidin-biotin complex technique using specific antisera made against full-length HBxAg polypeptide or derived synthetic peptides. These tissues were also stained for the HBsAg and HBcAg by the peroxidase-anti-peroxidase method. Among patients with chronic hepatitis, 86% were HBsAg positive in liver cells, 60% were surface antigen positive and 32% were core antigen positive. Among patients with cirrhosis, 97% were HBsAg positive in liver cells, 72% were surface antigen positive and 17% were positive for core antigen. Staining specificity was demonstrated, in part, by using preimmune sera in the place of primary antibody, by blocking of the primary antibody with the appropriate antigen before assay and by testing uninfected liver controls. The persistence and high frequency of HBxAg in liver cells from patients with chronic liver disease suggest that it may play one or more important roles in the pathogenesis of chronic infection. It is possible that detection of HBxAg in the liver could be an additional new diagnostic marker for hepatitis B virus infection. However, the function(s) of HBxAg in the pathogenesis of the chronic liver disease, if any, remains to be explained.

Pólipos de colon y recto. Síndromes de poliposis gastrointestinal

Se revisan las historias de 94 pacientes de la práctica privada entre los años 1950 y 1990 con pólipos del colon (71) y poliposis múltiple familiar (23). Se analizan diversos factores como el sitio de presentacion más frecuente, la sintomatología y su relación o no con carcinoma del colon. Se hacen consideraciónes sobre el tipo de conducta que debe seguirse de acuerdo con el hallazgo histopatológico. Los resultados muestran que la sintomatología de los pólipos en el adulto es muy pobre (54 por ciento asintomáticos), a diferencia de las juveniles donde la rectorrafia se presenta en el 96 por ciento de los casos. Un alto porcentaje de ellos se puede extraer por medios endoscopicos y el estudio completo del paciente debe extenderse al medio familiar determinando asi en forma precoz un diagnóstico y tratamiento adecuados de afecciones que potencialmente resultan malignas