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NZW rabbits with acute serum sickness given Cyclosporin A (CyA) 25 mg/kg/day develop glomerular capillary thrombosis similar to that seem in the haemolytic uraemic syndrome (HUS). Bone marrow recipients treated with CyA may also develop a similar renal lesion associated with a haemolytic uraemic-like syndrome. In the HUS, impaired production of prostacyclin by vascular tissue may be found and has been associated with a lack of a plasma factor which stimulates prostacyclin synthesis. We therefore examined, in six normal rabbits, treated with CyA 25 mg/kg for five days, the ability of plasma from treated and untreated rabbits to stimulate prostacyclin synthesis from normal rabbit aortic rings. Plasma from untreated rabbits produced 21.5 +/- 6.9 ng 6-keto PGF1 alpha/ml/mg wet weight aorta (mean +/- SEM). However, the ability of plasma from CyA-treated rabbits to stimulate prostacyclin production was profoundly reduced. This was apparent within 24 hours of starting and persisted for seven days after therapy was stopped: mean of values from all rabbits bled from start of therapy until seven days after therapy stopped was 3.7 +/- 0.5 ng/ml/mg. We suggest that the renal complications of CyA therapy are related to a failure of normal vascular prostacyclin synthesis due to lack of a prostacyclin-stimulating plasma factor.

Summary Epstein-Barr virus (EBV) DNA sequences were detected in four established monoblast or early monocytic cell lines (CM-S, ROV-S, CV-S and AD-S) obtained from bone marrow of children suffering from maturation defects of haematopoiesis. EBV is present in these cells in a latent state. The viral DNA in these cell lines was analysed by Southern blot hybridization, using a set of cloned EBV DNA fragments from the EBV strain B95-8 as probes. A common spectrum of highly related but distinguishable EBV DNA restriction enzyme sequences was found, suggesting some genomic diversity. Propagation of the cells in long-term culture revealed a gradual decrease of EBV copies per cell in all lines with some minor changes in the restriction pattern of the EBV DNA. These findings demonstrate that human precursor monocyte cells may be susceptible to infection by EBV.

Ultrastructural modifications are described in the plasma membrane of in vitro established human B cells. By the freeze-fracture technique, intramembrane particles (IMPs) are quantified in B lymphocytes following Epstein-Barr virus (EBV) transformation in vitro, and in B-lymphoma (Burkitt-type) cells, either positive or negative for EBV genome. Analysis shows an overall increase in IMP density as compared to normal controls. Differences are observed between the protoplasmic and exoplasmic faces of fractured membranes as well as among in vitro transformed and clearly neoplastic cells. Results indicate that conformational changes in IMP distribution parallel neoplastic evolution of transformed cells.

Antibody reactivity to Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) was investigated by means of the anticomplement immunofluorescence technique on sera from patients with Hodgkin's disease (HD) and from appropriate controls. Antibody levels to other EBV-determined antigens, i.e. viral capsid (VCA) and early antigens (EA), and to measles and rubella viruses, to cytomegalovirus (CMV), and to toxoplasma gondii were also measured. The results of anti-EBV antibody titrations demonstrated that anti-VCA, anti-EA and anti-EBNA reactivity was significantly higher in HD patients than in healthy subjects. There was no significant difference between the distribution of high rubella and measles antibody titers in HD and control sera. The GMT and the incidence of high titer anti-CMV and toxoplasma antibodies were greater in HD patients than in controls. The analysis of the data, according to histological subtypes, showed that the condition of lymphocyte depletion was associated in HD patients with the highest anti-EBNA antibody levels and the lymphocyte predominance with the lowest. This pattern seemed to be peculiar for anti-EBV reactivity, since anti-CMV and anti-toxoplasma antibody levels in the lymphocyte-depleted group of patients did not significantly differ from those of controls. No correlation was found between anti-VCA and anti-EBNA in individual sera of HD patients. This observation suggests that different mechanisms are probably responsible in HD for the release of EBV-related antigen from infected cells.

It has been demonstrated that peripheral blood lymphocytes, particularly the ‘atypical’ ones, are predominantly of the T type in infectious mononucleosis (IM). This is based on membrane marker studies (E rosettes, receptor for complement, receptor for Fc fragment of immunoglobulins (Ig), and membrane Ig) and by anti-T lymphocyte serum. On the other hand, lymphoblastoid cell lines derived from IM patients show the characteristics of B lymphocytes. This permits the supposition that EBV infects B lymphocytes and stimulates them to proliferate. The cell proliferation is unlimited in vitro and is probably controlled in vivo by T cells. The reduction of cellular immunity in vivo, which contrasts with the high number of T cells in peripheral blood, could be explained by the fact that T cells are engaged in the regulation of B cell proliferation.

In the present study the fine structures of Leu-7+-Leu-15+ and Leu-7+-Leu-15- cell subpopulations were characterized by using an immunogold-immunoperoxidase double labelling in electron microscopy. The densities of Leu-15 antigenic sites on both E rosetting (Er) and non-adherent/non-E rosetting (non-A/non-Er) Leu-15 positive cell surfaces were also evaluated by using an immunogold analysis in electron microscopy. A majority of Leu-7+ cells co-expressed the Leu-15 antigen and showed an ultrastructural pattern specific for mature natural killer (NK) cells, i.e. abundant cytoplasm with many organelles, numerous electron dense granules, and irregular outline. On the other hand, a minority of Leu-7+ cells did not express the Leu-15 antigen and showed a clearly different ultrastructural feature in comparison to Leu-7+-Leu-15+ cells. Thus, the presence of the Leu-15 antigen on Leu-7+ cell surface corresponds to ultrastructural features specific to differentiated NK cells and may represent an expression of Leu-7+ cell differentiation. An alternative hypothesis may be that Leu-7+-Leu-15+ and Leu-7+-Leu-15- cells represent distinct cell lineages within non-A/non-Er Leu-7+ cells. Finally, the results of the present study provide proof that Leu-15 antigen is more frequently represented on non-A/non-Er Leu-15+ cells than on Er Leu-15+ cells.

1. 1. The metabolism of pregnenolone-7α- 3 H and progesterone-4- 14 C was studied in the ovary and fat bodies of Triturus cristatus carnifex . The effect of ovariectomy and fat bodies asportation was examined. 2. 2. From the values of the ratio 3 H/ 14 C for testosterone it appears that in the ovary the biosynthetic pathway may go through pregnenolone → 17 α-hydroxypregnenolone → dehydroepiandrosterone , while in the fat bodies the preferential pathway is pregnenolone → progesterone → 17 α-hydroxyprogesterone . 3. 3. The amounts of 17 α-hydroxypregnenolone formed by the ovary are much higher than those synthesized by fat bodies. 4. 4. The ovary of fat-body-deprived animals show a different trend with time of 17 α-hydroxypregnenolone and dehydroepiandrosterone formation, while ovariectomy causes a decrease of dehydroepiandrosterone in the fat bodies.

SummaryA survey has been carried out (using Quinacrine stain) on the frequency and position of an intensely fluorescent body (F-body) in the nuclei of leukocytes from peripheral blood smears in normal individuals and in the main syndromes from numerical alteration of sexual chromosomes.

New ICRF (Ion Cyclotron Range of Frequency) antennas, targeted to reduce impurity generation in the all-metal ASDEX Upgrade were designed and fabricated at different sites in an international cooperation between IPP, ASIPP (Hefei, China) and ENEA (Frascati, Italy). Installation and test were done by a multinational team at IPP. The antenna further integrates a powerful reflectometer system, designed and built by ENEA and IST (Portugal). The project, with the cooperation of four institutes in four countries on two continents was successfully completed within budget and schedule boundaries. Test results, gathered during recent experiment campaign, reveal that the new antennas have achieved their goal: A significant reduction of ICRF heating induced W impurity generation at the antennas.

Serial sera from nine volunteers, injected 10 years ago with sheep erythrocytes and showing heterophile antibody responses comparable to those seen in infectious mononucleosis, were retrieved from storage and examined for antibodies to Epstein–Barr virus (EBV) related antigens. Eight of the nine volunteers had pre-existing antibodies to EBV, as determined by neutralization tests and by indirect immunofluorescence reactions with fluorescein-conjugated antibodies to human IgG, but not with anti-human IgM conjugates. The EBV-specific reactivities remained unchanged after immunization. The results indicate that: (a) EBV- or EBV antigen-containing lymphoblasts from carrier or freshly infected cultures contain no detectable heterophile antigen; (b) immunization with sheep erythrocytes does not evoke antibodies which interact with EBV or EBV-infected cells. These points are supported especially by the results obtained with the heterophile antibody-positive, anti-EBV-negative serum of one of the volunteers who subsequently sustained a primary EBV infection. It is unlikely, therefore, that immunization with heterophile antigen will induce immunity to infectious mononucleosis, apart from the fact that heterophile antibody responses are largely restricted to the IgM class.

A statistical study of the mortality from all causes and from respiratory diseases was carried out in an evaluation of the influenza epidemics in Italy from 1956 to 1973. Type A influenzaviruses were responsible for outbreaks every 2-3 years. Type B influenzavirus appeared every 4 years and accounted for a single noteworthy epidemic in 1962-63. From the analysis of data on both general mortality and respiratory mortality a better evaluation of the extent of the influenza outbreaks could be made.

Antibody response of 68 healthy young-adult volunteers to A/Bangkok/1/79 (H3N2), A/Brazil/11/78 (H1N1), B/Singapore/222/79 trivalent anti-influenza virus vaccine was studied by haemagglutination inhibition and single radial haemolysis techniques. The results of this study indicate that immunogenicity of the individual components of the vaccine (10 micrograms each) varied significantly, the highest frequence of antibody response occurring for A/Brazil influenza virus strain and the lowest for B/Singapore.

The CM-S cell line was established from the bone marrow of a child with congenital hypoplastic anemia and resembles its monocyte-macrophage lineage. Lethally x-irradiated CM-S cells from various passages and clones, representing different stages in the progression of the transformed growth phenotype, were tested for their ability to affect the survival and proliferation of normal human cord or adult blood leukocytes in co-culture. One clone, CM-SM, which is tumorigenic in athymic mice, consistently immortalized umbilical cord mononuclear cells but did not immortalize adult peripheral blood leukocytes. Six autonomous monocyte-like diploid cell lines were obtained and all were found to be of cord origin. Three lines were tumorigenic in athymic mice. Attempts to immortalize human leukocytes with cell-free supernatants from CM-S cells were unsuccessful.

Seventy-five young recruits received an intramuscular dose of anti-influenza virus vaccine containing 300 U.I. of A/Texas/1/77 (H3N2), A/URSS/90/77 (H1N1), B/Hong Kong/8/73 strains. Antibody responses were detected by HI and SRH tests: immunogenicity of the preparation was different for the individual vaccine strain in spite of the similar amount of antigenic content, and the immunity conferred by vaccine strains did not significantly extend to new influenza virus strains which prevailed in 1979/80 winter season with the exception for A/Brazil/11/78 (H1N1).

Several prospective methods for surveillance of influenza are systematically carried out among the population of this city: (a) monitoring of excess deaths from respiratory and other causes; (b) monitoring of excess absenteeism from work; (c) attempts to cultivate influenza virus from throat swabs obtained from patients with respiratory diseases attending outpatient services; (d) checking of increased antibody reactivity for prevailing influenza virus strains in serum samples obtained from healthy adults of the open population. The results of these studies will be reported with respect to influenza activity in the metropolitan area in the winter of 1976-1977. Comparison of the speed and effectiveness with which the influenza epidemic was identified in the urban population by the various surveillance methods will also be given.

The isolation of a measles-like virus in CV-1 cell cultures from a biopsy specimen obtained from a case of subacute sclerosing panencephalitis (SSPE) is reported. Evidence of the presence of cell-free virus was obtained from the fifth cell culture passage of the isolated virus. The virus was identified as measles-related by standard immune sera. IF study did not show relevant differences between the isolated virus and the Edmonston strain of measles virus, even though the proportion of cells showing nuclear antigen was higher following the infection with the isolated virus than with the Edmonston strain. Electron microscopy study failed to demonstrate viral structures in the cells from the brain biopsy, while numerous large aggregates of nucleocapsids were found in the cytoplasm of infected cells observed on the third and fourth passage in tissue culture. The neuropathogenicity assay carried out on newborn hamsters, rats and mice using a suspension of disrupted infected cells did not show any clinical pathological effect due to the SSPE strain. These results are partially in contrast with previous findings which indicate relevant differences in the morphology and pathogenicity of SSPE derived strains as compared to reference measles virus.

An outbreak of "hand-foot-and-mouth disease" (HFMD) occurred in Nov. 1973 in a nursery school. Sixty-seven children were studied, 15 of whom presented clinical signs of the disease. Sixty-two percent of the HFMD cases and 18% of asymptomatics were proved to be infected with Coxsackie virus A 16. The ratio of clinical to asymptomatic infection of nursery-school children with confirmed Coxsackie A 16 infection was 58%. The accidental diffusion of the infection led to the occurrence of secondary cases. This allowed to establish the incubation period of the illness at 8 to 12 days, for 3 individual cases where a single infecting contact in a very definite time could be documented. Fecal excretion of virus was demonstrable in 2 cases up to 10-20 days, while the duration of oral excretion appeared to be somewhat shorter. Evidence was also obtained showing that infectious virus could be spread by patients during the incubation period. Virus isolations were more easily obtained in suckling mice than in cell culture.

We describe the case of a young woman affected by systemic high blood pressure, in whom the clinical history and laboratory data (hypokalaemia, low plasma renin activity and negligible aldosterone levels) were consistent with the hypothesis of liquorice-induced hypertension. After six months of abstinence from liquorice, all laboratory data returned to normal levels, but blood pressure remained elevated. This unusual persistence of liquorice-induced hypertension supports the hypothesis that liquorice facilitated the phenotypic development of a hypertensive state in a patient with a family history positive for that disease.

The relationship between the diaphragmatic hiatus, the infra-diaphragmatic esophagus and a manometric tube were examined in 10 patients not suffering from hiatal hernia or gastroesophageal reflux. During surgery, two metal markers were attached to the diaphragmatic hiatus and two others were fixed at the vertex of the angle of His. X-ray examinations were taken during manometric recordings of the high pressure zone (HPZ) both at rest and during relaxation. Comparison between the radiographs showed that during swallowing the manometric tube did not move with respect to the vertebral bodies; contraction of the esophagus caused complete disappearance of the infra-diaphragmatic esophagus. It was also observed that during pressure drop in the HPZ (so-called lower esophageal sphincter relaxation), the manometric recording site is located below the vertex of the angle of His, i.e. in the gastric cavity. These findings provide the basis for a hypothesis to explain the passage of a solid bolus through the lower esophagus into the stomach.

Since 1-(m-chlorophenyl)piperazine (mCPP) is a metabolite of trazodone (TRZ) and etoperidone (ETO), two atypical antidepressants, a pharmacological study was undertaken to establish the possible contribution of mCPP to the effects of the parent compounds. Behavioral effects of mCPP in rats consist in head shakes and other signs of serotoninergic stimulation; subtoxic doses also produce clonic convulsions and prostration. TRZ and ETO produce sedation and signs of alpha-adrenergic blockade; subtoxic doses produce tremors, clonic convulsions and prostration. Peripheral effects of norepinephrine (NE) and serotonin (5-HT) in rats are potentiated by mCPP and inhibited by TRZ and ETO. 5-hydroxytriptophan (5-HTP)-induced head twitches in mice are inhibited by TRZ and ETO and unaffected by mCPP. At similar doses mCPP, TRZ and ETO inhibit some nociceptive responses in rats and mice.

An epidemiological study was carried out in a juvenile diabetics institution, in order to determine the incidence and the significance of the hepatitis associated Australia antigen (HBAg) carriers. By means of counterelectrophoresis and CF an average of 15% HBAg-positive individuals was found during the course of the search (June 1970-January 1973). As a rule the carrier state appeared to be longlasting and it was only occasionally associated with symptoms and/or signs of liver involvement. Isolation measures to inhibit spread of serum hepatitis (the hepatitis most associated with HBAg) failed partially to prevent the spread of the HBAg associated agent suggesting that nonparenteral transmission could play a role in the diffusion of the infection.

In September 1982, I (BSK) wrote to Dr. Conrad Gasser to inform him of my intention to dedicate this contribution to him. He died a month before my letter reached his office. Conrad Gasser not only separated haemolytic uraemic syndrome (HUS) from thrombotic thrombocytopenic purpura (TTP) but also defined its cardinal features (Gasser et al. 1955) and recognised that there could be familial occurrences, recurrences and the possibility of a favourable long-term prognosis. In paying tribute to Dr. Gasser, it is also fitting to mention the important contributions of Dr. Renee Habib and Dr. Carlos Gianantonio and their respective colleagues. Dr. Habib has made the most important contributions to our understanding of the renal histopathology of HUS (Habib et al. 1967, 1982), while Dr. Gianantonio’s descriptions of the clinical features of the “classical” form of HUS are unequalled, and he has led the way in the treatment of HUS by peritoneal dialysis (Gianantonio et al. 1964, 1967, 1973).

SUMMARYRotavirus infection was demonstrated in 168 (29·3%) of 573 children hospitalized for acute diarrhoea in Rome between January 1982 and December 1984. Laboratory diagnosis of these infections was made by transmission electron microscopy and enzyme immunoassay techniques with an overall agreement of 91·3%. Astroviruses, adenoviruses and small round viruses were detected in the faeces of 36 patients (6·4%). Whereas in 1982 rotavirus positive patients were clustered in the winter and following spring, in the following years cases were recorded all year round. The median age of patients with rotavirus infections was 17, 10 and 11·5 months in 1982, 1983 and 1984, respectively. In addition, a smaller number of rotavirus positive cases were admitted in 1983 when compared to those admitted during the previous as well as the subsequent years. It is suggested that a herd immunity was induced in the population by epidemic spread of rotavirus in the first half of 1982.

Data on hemoagglutination inhibition (HI) tests for rubella immunity which were performed in our laboratory since 1972, are reported. The results obtained on sera from healthy young women indicate a significant decrease of incidence of sero-negatives in 1978 as compared with previous years. The incidence of high titer-positive sera and the geometric mean titer of HI antibody were significantly greater in 1973 and 1978 than in the remaining years; a greater number of case reports to Public Health Authorities occurred in Rome during these two years. The data are also discussed in relationship with vaccination program.

The single radial haemolysis technique was employed for the detection of rubella antibodies. By using this technique, as compared with the conventional haemagglutination-inhibition test on the same serum samples, it was observed that the single radial haemolysis technique supplies a reliable method for large rubella antibody screening.

Immunoglobulins and virus-specific antibody in nasal secretions were measured in 18 volunteers before and after intra-nasal vaccination with two live-attenuated type A influenza virus strains. Specific serum antibody rises occurred in 14 out of 18 vaccinees; of those, 11 and 10, respectively, showed significant increase of IgA concentration and of virus-specific antibody in nasal secretions collected 2-4 weeks after vaccination. In one case, a volunteer showed appreciable increase of virus neutralizing antibody in nasal secretions without increase of local IgA concentration and of serum HI antibody. This data indicate that administration of live virus vaccines by upper respiratory route confers effective immunity associated with local antibody synthesis.

In the periods from July 1982 to June 1983 and July 1983 to June 1984, 31 strains of influenza virus, of which 19 A/H3N2 6 A/H1N1 and 6 type B, were isolated from 242 throat cultures obtained from patients with acute febrile respiratory disease. A seroepidemiological survey on 520 serum samples confirms significant activity of influenza viruses during the winterly period of 1983-1984. In the period July-August 1983 the evaluation of mortality from respiratory diseases presents an excess in respect of epidemic threshold probably ascribable to heat stroke.

This study was undertaken with the aim of elucidating the mechanisms underlying the cell-mediated immunodeficiency seen in the acquired immunodeficiency syndrome (AIDS). An intrinsic functional defect in the in vitro surviving T lymphocytes from patients with AIDS has been described. This defect is reflected by profound reductions in both the cloning efficiency of these cells and in the number of precursor cells for response to lectins. Since many patients affected by AIDS present active cytomegalovirus (CMV) infections and impairment in CMV-specific cellular immunity, we examined the number of CMV-specific precursor cells in patients affected by the AIDS-related complex (ARC), who had serum antibodies to CMV and to the human-T-lymphotropic retrovirus-type III (HTLV-III), recently termed human immunodeficiency virus (HIV). Their responses were compared to those of patients with AIDS and to those of healthy-CMV-seropositive and HTLV-III seronegative controls. We detected a significant reduction of precursors for cell-mediated immune response to CMV in AIDS, in comparison to normal controls and a reduction in ARC, even if not significant. In parallel, we assayed the response to phytohemagglutinin, which was maintained in ARC and depressed in AIDS. Our results show a defect of specific cell-mediated immunity to CMV in ARC and AIDS patients.

From nine day care centers in Rome, Italy, 253 children of middle to low socioeconomic classes were examined for cytomegalovirus (CMV) excretion in saliva. The overall excretion rate was 13%, with no marked differences between centers. Socioeconomic level, age of enrollment, chronological age, length of attendance, and number of siblings did not have any discernible influence on viral shedding. The most notable result is that during the second year of age, 100% of the excretors had been breast fed, but only 60% in the third year, indicating that maternal transmission is the most likely source of children's infection early in life. Serologic survey of 82 female workers in day care centers, 82 matched housewives, and 229 female students aged 14 to 18 years who were in training to care for children showed that at 14 years of age the CMV seropositivity rate is 85, which suggests that primary infection during childbearing age is an uncommon event in Rome.