Biomedical subjects
Publications and source records attributed to L Nespoli.
Four cases of multifocal osteomyelitis of unknown origin in childhood are reported. The variable clinical and radiographic appearances of the disease are illustrated and the diagnostic difficulties in the early stages of the disease are stressed.
It has been recently reported that cord blood lymphocytes (CBL) contain a subpopulation of OKT8+, sheep erythrocyte-rosetting negative (E-) cells not detectable in adult peripheral blood lymphocytes (a-PBL). The present studies were undertaken to characterize this subset of lymphocytes functionally and phenotypically. OKT8+ cells were purified from E-depleted CBL by negative selection on nylon-wool columns as well as by positive selection on plates coated with rabbit antibody to murine IgG (panning). The purified CBL displayed natural killer (NK) activity against K562 erythroleukemic cells. Although most of these CBL were large granular lymphocytes, they lacked typical NK markers such as HNK-1 and OKM1 surface antigens. Most OKT8+, OKT3- cells were also OKT10+, Ia+ and had the receptor for peanut agglutinin. These CBL may represent a stage along the differentiation pathway leading to mature NK or T cells.
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A new solid-phase immunoassay based on the biotin/avidin system (BAS) for measuring serum Lolium perenne (LP)-specific IgE antibody is described. LP-specific IgE was assayed by the BAS assay and RAST for comparison in the sera of thirty-two normal asymptomatic subjects RAST-negative for LP and of twenty-six subjects with hay fever and RAST-positive for LP. The specificity of the BAS assay for LP-specific IgE was demonstrated by absorption experiments. An overall agreement of 91% (53/58) was observed between the BAS and RAST and a high correlation (r = 0.87, P less than 0.001) was found between the LP-specific IgE determined by the two methods. The advantages of the BAS assay as compared to both the RAST and classical ELISA are discussed.
Peripheral blood lymphomononuclear cells (PBL) from 35 patients with Down's syndrome (DS, trisomy-21; 25 institutionalized and 10 non-institutionalized) were phenotypically characterized by means of various monoclonal antibodies. They included a high percentage of T lymphocytes with low avidity for sheep erythrocytes as well as an extremely high percentage of HNK-1+ cells and of lymphocytes reacting with the OKT8 and Leu 2a antibodies. The HNK-1+ cells of DS include four different subsets: (a) E+, OKT3+, OKT8-, Leu 2a-; (b) E+, OKT3+, OKT8+, Leu 2a+; (c) E-, OKT3-, OKT8-, Leu 2a- and (d) E-, OKT3-, OKT8+, Leu 2a+. Subsets (a) and (c) are also present in PBL from karyotypically normal controls while subsets (b) and (d) have a phenotype which has not been previously reported. These findings may be related to the triple expression by trisomic cells of the receptor for interferon, which is coded by a gene located on chromosome number 21. Alternatively, the high number of 'immature' NK cells of DS, possibly identical with pre-T lymphocytes, may originate from the congenital thymic derangement associated with trisomy 21.
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T cell subpopulations of lymphocytes from cord blood (CBL) of 24 newborns and from peripheral blood (a-PBL) of 24 healthy adult volunteers were assessed in T cell-enriched, T cell depleted and unseparated lymphocyte fractions by using OKT3, 4, 6, and 8 monoclonal antibodies. The results show that T cell-enriched CBL include adult numbers of OKT3+, OKT4+, OKT6+ and OKT8+ lymphocytes whereas the T cell-depleted fraction consists of a high percentage of OKT8+, OKT3-, non-E rosette-forming cells bearing a PNA receptor. The presence of the PNA receptor and the lack of the OKT3+ antigen strongly support the hypothesis that the subset of OKT8+ cells in cord blood includes immature T lymphocytes that may represent an intermediate stage between thymocytes and mature peripheral T cells.
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Colostral lymphocytes were studied using two established T-cell markers: intracytoplasmic alpha-naphtyl-acetate esterase (ANAE) staining and membrane receptors for sheep erythrocytes (E rosettes). ANAE staining allowed counting and identification of T-cell subsets independently of the status of membrane structures and receptors frequently altered in colostral cells. The fact that a sizeable number of colostral lymphocytes had the same phenotype as the majority of mature circulating peripheral blood lymphocytes supports the hypothesis that colostral lymphocytes may play a role in protecting neonates against infections, in transferring immune information to the newborn, or in modulating the immune response via release of soluble factors. A considerable percentage of colostral T lymphocytes are ANAE-negative. This phenotype is similar to that observed among thymocytes.
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The age-related variations in the growth-promoting activity of human plasma have been studied from birth (cord blood) to adulthood using a bioassay which measures the incorporation of tritiated thymidine into lectin-activated human lymphocytes. Cord blood values were low (0.69 +/- 0.004 U/ml). A definite increase was found at 5 days of age, correlating with the level at birth. Higher levels were attained after 1 month of age, with a 2-fold increase during the first months of life. Lower values were found in children 1-10 yr old, and high levels were found during puberty. This pattern, different from those of sulfation activity and plasma somatomedins suggests that factors other than somatomedins may be involved in growth stimulation during the first year of life in humans.
Immunological functions were studied in two 22-month-old dizygotic twins with the characteristic features of Shwachman syndrome. A severe defect of neutrophil motility was found in both children, but not in their parents. An impairment of the activity of the alternative pathway of complement was present in the sera of both patients. This defect, in association with the neutropenia and the chemotactic defect, might be related to the recurrent infections displayed by the twins.
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Serum immunoglobulin levels of 86 epileptic patients have been evaluated in order to investigate the relationship between epilepsy, antiepileptic drugs and humoral immunity. The results confirm a high incidence of immunological disorders in the epileptic and febrile convulsion patients. These abnormalities were not related to clinical type of epilepsy nor to the therapy; the common feature seems the early onset of seizures and antiepileptic treatment.
Fifty children with IgA deficiency were folllowed for 1 to 4 years from 1975 to 1978. Thirty-five had complete deficiency of serum IgA (less than 2.5 IU/ml) and 15 partial deficiency (serum IgA below the 10th centile for age). Patients with another associated immunodeficiency, such as ataxia-telangiectasia, were not included. Most children with complete deficiency of IgA had recurrent respiratory and/or gastrointestinal infections, about half with onset in the first year of life, while partial deficiency of IgA has probably little if any importance for anti-infectious immunity but is important in the pathogenesis of atopy. Atopic diseases were frequent in both groups. Chromosomal abnormalities were found in 2 patients: trisomy 21 in one and in the other a ring chromosome 18. No important defects in cellular immunity were detected but some isolated, borderline abnormalities were often present.
We studied the interaction of lipopolysaccharide (LPS) and concanavalin A (Con A) with regard to IgM and IgG production in in vitro cultures of human peripheral blood lymphocytes (PBL). In our system LPS alone over a wide range of concentrations did not stimulate detectable IgM or IgG production, while Con A at optimal (6 microgram/ml) and suboptimal (0.6 microgram/ml) mitogenic concentrations induced synthesis of small amounts of Ig. A marked enhancing effect was present when both Con A and LPS were added to the cultures. The different doses of LPS has similar effects on both classes of Ig, and typical dose-response curves were obtained. To evaluate the cellular basis of this synergism, the effect on cell proliferation was studied under identical experimental conditions in normal subjects and patients with X-linked agammaglobulinaemia (X-LA). Parallel cultures were set up after monocyte depletion by adherence on Petri dishes. On day 3, increasing doses of LPS were associated with progressive decreases in 3H-thymidine (3H-TdR) incorporation. Similar results were obtained with normal lymphocytes and those from X-LA patients. Monocyte depletion did not substantially alter the lymphocyte response pattern. The preferential induction of helper activities, either directly by helper stimulation or indirectly by suppressor inhibition, is suggested as a possible mechanism of the interaction observed.