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Biomedical subjects

D Nadal

Publications and source records attributed to D Nadal.

At least 109 records · Page 6Linked to original sources
PubMed1992

Direct demonstration of engraftment of human peripheral blood leukocytes in SCID mice.

One of the major problems using man-mouse chimeras is still the difficulty to demonstrate unequivocally engraftment of human cells in murine tissues. Using supravital labelling of human leukocytes with the Hoechst dye H33342, it was possible to demonstrate directly their engraftment and to assess their distribution in the tissues of the severe combined immunodeficiency (SCID) mice. The human cells can be traced for a period of 4-5 weeks. In contrast to earlier reports, combined marker and labelled-cell studies suggest that T-cell surface marker CD3 with reported specificity for human lymphocytes are indeed found, also in man-mouse chimeras, only on human cells. The ratio of B and T cells of human origin changes significantly after transfer into SCID mice and differs among various SCID tissues. The simple staining procedure using the supravital nuclear dye H33342 opens new possibilities for the study of cellular interactions and host responses of the human immunoreactive cells in an increasingly well-characterized animal model.

Animals↗
PubMed1992

Immunologic response of adenoidal lymphocytes to respiratory syncytial virus.

Adenoidal lymphocytes obtained from 43 subjects with serum antibodies to respiratory syncytial virus (RSV) were established in culture in vitro and analyzed for immunoglobulin (Ig) and RSV-specific antibody synthesis. Spontaneous synthesis of Ig was consistently observed in culture supernatants. The ratios of IgA to IgG and IgM to IgG in adenoidal lymphocyte culture supernatant were higher than in serum. In cell cultures stimulated with RSV or pokeweed mitogen, RSV antibody activity was detected in 25 of 43 (58.1%) for IgG, 5 of 43 (11.6%) for IgA, and 4 of 43 (9.3%) for IgM. Also, RSV-specific IgG was detected in some supernatants from unstimulated cultures. In seven cases the cultures of autologous tonsillar lymphocytes were also investigated. Autologous organs exhibited similar polyclonal Ig production and RSV-specific antibody synthesis. These observations demonstrate that both adenoids and palatine tonsils are continuously engaged in synthesis of local antibodies to viral pathogens available to the nasopharynx and respiratory mucosa.

Adenoids↗
PubMed1991

Tissue distribution of mucosal antibody-producing cells specific for respiratory syncytial virus in severe combined immune deficiency (SCID) mice engrafted with human tonsils.

Groups of C.B-17 SCID mice were reconstituted intraperitoneally with human tonsillar mononuclear cells (hu-TMC) from children seropositive for antibody to respiratory syncytial virus (RSV) and subsequently challenged intraperitoneally with inactivated RSV or sham-immunized. The synthesis and the distribution characteristics of human antibody to RSV in various murine tissues were studied using an enzyme-linked immunospot assay (ELISPOT). No specific antibody was observed in sham-immunized animals. In contrast, mice engrafted with hu-TMC exhibited the appearance of specific human antibody secreting cells (hu-ASC) after i.p. immunization with inactivated RSV. RSV-specific hu-ASC were detected only in animals engrafted with cells from donors seropositive for antibodies to Epstein-Barr virus. Hu-TMC engrafted mice showed RSV-specific IgM and, in lower numbers, IgG hu-ASC in several tissues including the lungs. Numbers of RSV-specific IgA hu-ASC were low, however, and detected only in the lung. No RSV-specific hu-ASC were detected in the intestine. These data demonstrate for the first time that hu-TMC-SCID chimeras respond to immunization with viral antigen. Furthermore, the results suggest that hu-TMC engraft in lungs but not in the intestinal tissue.

Adolescent↗
PubMed1991

Distribution and engraftment patterns of human tonsillar mononuclear cells and immunoglobulin-secreting cells in mice with severe combined immunodeficiency: role of the Epstein-Barr virus.

Tonsils seem to be the ideal source of lymphocytes seeding to the mucosa of the respiratory tract. The distribution and engraftment of human lymphocytes injected into mice with severe combined immunodeficiency (SCID) are not well understood. C.B-17 SCID mice were injected intraperitoneally with human tonsillar mononuclear cells (hu-TMC). The hu-TMC-SCID mouse chimeras were subsequently tested for the appearance and distribution of human lymphocytes tagged with H33342 and immunoglobulin-secreting cells in various systemic and mucosal immunocompetent tissues. This was done by fluorescence microscopy of tissue sections for cells supravitally stained before transfer and by an enzyme-linked immunospot assay using cells isolated from murine organs. Most importantly, engraftment of hu-TMC proved to be dependent on the presence of anti-Epstein-Barr virus (EBV) antibody in the donor. hu-TMC engrafted, in decreasing numbers, in the following systemic organs: peritoneal cavity, liver, spleen and bone marrow. Among mucosal tissues tested, hu-TMC were seen in lungs, but not in the intestines. The engraftment of hu-TMC in the lung was more extensive than that in the spleen. These studies demonstrate that hu-TMC engraft in a variety of murine tissues. The striking preference of hu-TMC for the lungs when compared to intestines suggests selective engraftment among distinct mucosal tissues. The hu-TMC-SCID mouse chimera promises to be a unique animal model to study human-mucosa-associated lymphoid cells and EBV-related lymphomagenesis and B cell tumor progression.

Adult↗
PubMed1990

Acute mastoiditis: clinical, microbiological, and therapeutic aspects.

The charts of 73 children (31 girls, 42 boys) aged 4 months to 14 years (mean 4.5 years) with acute mastoiditis managed during a 16-year period were reviewed. Of the patients 36% were less than 24 months old. Retro-auricular swelling was described in 63 of the 73 children, tenderness in 59, erythema in 58, and protrusion of the auricle in 45. A pathological tympanic membrane was noted in 33% of the patients and fever in only 29%. Apart from local inflammation, the most frequent complaints and symptoms were otalgia (n = 42), recent upper respiratory tract infections (n = 22), and fever alone (n = 22). A subperiosteal abscess was found in 36 patients, and CNS involvement in 5. Nearly half of the patients (48%) were on antibiotic therapy at admission. The isolation rates in bacterial cultures from subperiosteal aspirated (81%) and from mastoid mucosa (68%) were considerably higher than from blood cultures (14%) and were not influenced by previously administered antibiotics. Pneumococci (9/32) and Staphylococcus epidermidis (6/32) were the agents most often isolated. The incidence of the bacteria isolated from patients pre-treated with antibiotics differed from the incidence in patients not previously treated. In 24 patients (33%) the lesion healed with antibiotic therapy without mastoid surgery. Myringotomy and the insertion of a ventilation tube is indicated initially, if acute otitis media with effusion is found. In the absence of a subperiosteal abscess and of CNS involvement, a 48-hour trial of intravenous antibiotic therapy, directed also against staphylococci, is justified before mastoid surgery is considered.

Abscess↗
PubMed1990

Development of local immunity: role in mechanisms of protection against or pathogenesis of respiratory syncytial viral infections.

The bronchus associated lymphoid tissue (BALT) and the precursor immunocompetent lymphoid cells in the nasopharynx, tonsils, and salivary glands represent the basic source of specific secretory IgA, other immunoglobulin, and T cell mediated specific immunity in the respiratory tract. The bulk of this immunologic reactivity is derived largely from BALT, and via the migration of antigen-sensitized immunocompetent cells, from the gut associated lymphoid tissues (GALT). Recent investigations have suggested that mechanisms underlying the development of virus-induced bronchopulmonary diseases, notably bronchospasm, include host factors such as altered immune response with persistent virus-specific IgE and IgG4 antibody responses in the respiratory tract, the appearance of specific immune complexes, and development of exaggerated immune response to other environmental agents and dietary proteins. In addition, pathogen related factors responsible for direct tissue damage during infection also play an important role.

Adolescent↗
PubMed1989

Stable human immunodeficiency virus encephalopathy in two infants receiving early intravenous gammaglobulin plus antimicrobial prophylaxis.

Two infants with human immunodeficiency virus (HIV) infection, encephalopathy, intrathecal anti-HIV IgG antibody production and (in one case) the presence of HIV antigen received monthly doses of intravenous gammaglobulin (IVGG) and daily antimicrobial prophylaxis starting at the ages of 6 and 9 months respectively. The follow-up over 15 and 12 months revealed a favourable course with remarkable improvement in visuo-spatial functions, receptive language, play behaviour and fine motor skills, as well as in muscle tone, pyramidal tract signs and vigilance in case 1, and near normalization in case 2. Viability of HIV in peripheral blood mononuclear cells, antigen in serum and cellular immunodeficiency, however, all remained unchanged. We suggest that neurological complications of encephalopathy in paediatric acquired immunodeficiency syndrome may have a slower progression when IVGG treatment plus antimicrobial prophylaxis is started early.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Infants born to mothers with antibodies against Borrelia burgdorferi at delivery.

A serological survey over a 1-year period of 1416 mothers at delivery and their 1434 offspring for the presence of anti-Borrelia burgdorferi antibodies revealed a prevalence of 0.85%. Clinically active Lyme disease during pregnancy was found in 1 of these 12 women with elevated titres and the child was born with a ventricular septal defect. Of six affected children, two had hyperbilirubinaemia, one muscular hypotonia, one was underweight for gestational age, one was macrocephalic, and one had supraventricular extrasystoles. Anomalous findings could not be attributed to B. burgdorferi due to a lack of serological evidence of intrauterine infection. Our data do not imply the need for serological screening in pregnancy, however, the importance of recognition and treatment of Lyme disease in pregnancy is emphasized.

Adult↗
PubMed1989

Prevalence of antibodies to Borrelia burgdorferi in forestry workers and blood donors from the same region in Switzerland.

Sera from 259 forestry workers and 100 blood donors in the Canton of Solothurn, Switzerland, were tested for IgG antibodies to Borrelia burgdorferi in two EIAs using as antigen either sonic extract of whole organisms or purified flagella. Applying a 95% specific cut-off value based on results in the sera of 100 blood donors, 86 (33%) and 91 (35%) of the forestry workers respectively showed an elevated specific IgG level in the two EIAs. None of the 259 forestry workers had clinical signs of active infection at the time blood was taken, and only nine could recall experiencing erythema-migrans-like skin lesions within the last ten years. Thus, asymptomatic infections must be frequent. Elevated specific antibody levels increased significantly with the age of the forestry workers (p less than 0.0001) and the duration of occupational exposure to ticks (p = 0.0001). Thus serological results in individuals with high exposure to ticks must be interpreted with caution in view of the high a priori prevalence of antibodies to Borrelia burgdorferi in such persons. The prevalence of antibody to the Borrelia burgdorferi flagellum in a control population not selected for tick exposure, in this case blood donors, seems to be independent of geographical origin.

Adult↗
PubMed1989

Immunological evaluation in the early diagnosis of prenatal or perinatal HIV infection.

A longitudinal evaluation was carried out of the clinical, infective, and immunological progress of 34 children (who were aged 6 to 68 months--mean 25 months at the time of writing) born to 31 mothers infected with human immunodeficiency virus (HIV), over a mean observation period of 13.4 months. Clinical symptoms, not always clearly related to HIV became apparent in 11 children, and preceding immune abnormalities were documented in two of them. In eight children culture for HIV was positive, and six of these were symptomatic. No cancers were diagnosed and none of the children died. Immune abnormalities including hypergammaglobulinaemia, IgG subclass deficiency, low serum IgA concentration, antibody deficiency, a decrease in the number of CD4+(T helper) cells, and defective cellular responses to antigens, were found in seven of the children in whom culture for HIV was positive; in two of four who had symptoms and in all four who were symptom free and in whom culture was negative for HIV but in whom HIV antibodies persisted and who were older than 15 months; and in three of nine who were symptom free and in whom culture was negative with loss of HIV antibodies. We conclude that serological diagnosis alone may be misleading and that additional immunological assessment may help to identify affected children. Analysis of humoral and cellular responses to antigens used for vaccination such as tetanus toxoid by measurement of specific antibodies and skin testing are simple and helpful in clinical practice.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Tumour necrosis factor-alpha in infectious meningitis.

During a one year period tumour necrosis factor-alpha (TNF-alpha) was prospectively determined in the cerebrospinal fluid of 49 patients with infectious meningitis. TNF-alpha was found in the cerebrospinal fluid of 15 of 18 patients with bacterial meningitis. In 11 patients who had cerebrospinal fluid positive for TNF-alpha it was detected in only one serum (in low concentration). There was no significant correlation between the concentration of TNF-alpha in cerebrospinal fluid and the patient's age, duration of illness and fever, body temperature, and serum C reactive protein. However, cerebrospinal fluid protein concentrations of greater than or equal to 2 g/l and leucocyte values of greater than or equal to 2.5 X 10(9)/l were more often associated with high TNF-alpha concentrations (greater than or equal to 500 pg/ml). In contrast with bacterial meningitis, none of the 31 samples of cerebrospinal fluid from patients with viral meningitis was positive for TNF-alpha. Thus this investigation supports the conclusion, drawn from animal studies on TNF-alpha in the cerebrospinal fluid, that the presence of TNF-alpha is indicative of bacterial meningitis. Absence of TNF-alpha cerebrospinal fluid, however, was found here not to exclude a bacterial aetiology of the infection.

Adolescent↗
PubMed1989

Immunoblot analysis of antibody binding to polypeptides of Borrelia burgdorferi in children with different clinical manifestations of Lyme disease.

We analyzed by means of immunoblot technique the patterns of antibodies binding to polypeptides of Borrelia burgdorferi B31 in the sera of 21 children with different stages of Lyme disease. All sera but one recognized the flagellar protein 41 kD and all but two the 83-kD protein. The number of proteins recognized rose from clinical stage I to stage III. The polypeptides of the mol wt 55 and 31 kD were exclusively bound by IgM and the proteins 66, 58, 39, and 36 kD exclusively by IgG. Based on the number of proteins visualized by single sera, IgM was the predominant isotype in stages I and II peaking in stage II, whereas in stage III IgG predominated. Considering the number of proteins recognized and the corresponding antibody isotype, a serologic differentiation between the three stages of the disease is feasible: within stage I and within stage III patients with different clinical signs had distinct antibody patterns. No clearcut pattern could be discriminated in stage II for patients with different settings. Immunoblotting yields a possible distinction between active infection and serological scar by the detection of specific antibody patterns.

Adolescent↗
PubMed1989

[Listeriosis in the newborn infant: improved prognosis due to early detection].

Perinatal clinical data were collected retrospectively from 35 newborn infants infected with Listeria monocytogenes and compared with the subsequent outcome. The average annual incidence of neonatal listeriosis in the Canton of Zurich (Switzerland) between 1983 and 1987 was 0.33 per 1000, which is more than twice that during the preceding 10 years. This increase paralleled a similar outbreak in the French part of Switzerland, where contaminated soft cheese was found to be the source. Three infants were probably cross-infected in the delivery room. Antenatal symptoms included fever in the mother, greenstained amniotic fluid, pathological cardiotocogram, premature contractions and disappearance of fetal movements. After birth the infants showed respiratory distress, fever or hypothermia, exanthema or neurological abnormalities. A gram stain of the gastric content was highly accurate in predicting listeria infection (92% sensitivity, 90% specificity). Five infants died, all within 24 h of birth; seven infants survived with and 23 without, sequelae. Factors associated with fatal outcome were a short gestational age, a low birth weight and a long interval between onset of symptoms and delivery or first dose of an appropriate antibiotic. Cephalosporins were not effective in four infants and therefore should not be given alone to pregnant women and newborn infants as long as Listeria monocytogenes infection is not excluded.

Adult↗