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Biomedical subjects

Z T Handzel

Publications and source records attributed to Z T Handzel.

36 records · Page 2Linked to original sources

Is common variable hypogammaglobulinemia linked to HLA? A family study.

Two patients with common variable hypogammaglobulinemia (CVH) and their families, who came from different ethnic backgrounds, were surveyed for the level of immunoglobulins (Ig) and HLA genotypes. Six of 10 siblings and the mother in one family had a decreased level of one of the major classes of Ig (IgA in 5, IgM in 1 and IgG in the mother). A similar decrease was found in three of six siblings in the other family (IgG in one, IgA in one and IgM in one). HLA genotyping disclosed that affected and nonaffected family members had identical genotypes, suggesting that hypogammaglobulinemia in CVH is not linked to a specific HLA genotype.

Adolescent

Effect of thymic humoral factor on cellular immune factors of normal children and of pediatric patients with ataxia telangiectasia and Down's syndrome.

Cellular immune functions of nine Down's syndrome patients and of nine was Ataxia telangiectasia vs. nine normal children and nine cord bloods, were evaluated using in vitro assays of peripheral blood lymphocytes. The in vitro assays included E rosette formation, antilymphocytic cytotoxicity by an antithymic antiserum and leukocyte migration inhibition factor (LIF) production. The mitogens and antigens used were phytohemagglutinin, purified protein derivative, and monilia antigen. The effect of a thymic hormone (THF) on these parameters was evaluated and it was administered therapeutically to three Down's syndrome patients and to two patients with Ataxia telangiectasia. Most deficient T-cell functions were reversed to normal after incubation of the lymphocytes with THF, or after THF therapeutic administration. In two Down's syndrome cases, the clinical course was not altered by THF administration, while one seemed to benefit from it markedly. One of the Atactic patients recovered from a severe viral infection, while the other died from intractable bronchopneumonia.

Ataxia Telangiectasia

Participation of a histamine-Sepharose-adherent subpopulation of human mononuclear cells in the production of leucocyte migration inhibition factor (LIF) in healthy children.

The separation of mouse splenic T lymphocytes into distinct subpopulations by fractionation on histamine-rabbit serum albumin Sepharose (H-RSAS) columns has been described. The H-RSAS-adherent T cells have been attributed regulatory functions associated with B cell activity, T cell-mediated cytotoxicity and the secretion of mediators such as immuno-interferon. The possibility that H-RSAS-adherent T cells exert a similar regulatory effect on an in vitro parameter of T cell-mediated immunity was investigated by assaying the production of leucocyte migration inhibition factor (LIF) in human blood samples, using the agarose droplet method. Phytohaemagglutinin (PHA) and BCG-purified protein derivative (PPD) were used as stimulants of LIF secretion which was measured as a percentage of inhibition of linear leucocytic migration. In normal individuals a highly significant (P less than 0.001) decrease was demonstrated in the production of LIF by peripheral blood leucocytes depleted of H-RSAS-adherent cells. Migration inhibition dropped from 36 +/- 11.7% to 21.2 +/- 12.9% in eighteen cases tested with PHA and from 29.3 +/- 11.7% to 17.2 +/- 9.8% in twelve cases tested with PPD. These results suggest the existence of a lymphocytic subpopulation involved in LIF production which expresses histamine receptors.

Cell Adhesion

An in-vitro immunological assay for diagnosis of coeliac disease.

Production of leucocyte-migration-inhibition factor (L.I.F.) by peripheral-blood lymphocytes in response to challenge with gluten fractions was studied in 55 patients with coeliac disease and in 32 controls. 96% of the patients with coeliac disease demonstrated significant L.I.F. reaction in response to gluten fractions irrespective of their dietary status. Only 2 out of 32 controls had a positive reaction. This was in response to the B2 or B3 fraction, but never to both. The agarose microdroplet method of L.I.F. assay is reliable and technically simple enough for use in most clinical laboratories. The assay of L.I.F. production by peripheral-blood lymphocytes in response to gluten fractions, would be a useful adjunct in the diagnosis of gluten-sensitive enteropathy.

Adolescent

Immune deficiency of T system with possible T cell regulatory activity defect.

The occurrence of T system immunodeficiency in an infant together with excessive production of IgM and, to a lesser degree, of IgG and IgA, is an unusual combination. A case is reported in which an unremitting lung infection with lymphadenopathy and hepatosplenomegaly developed in a previously healthy two-month-old infant. Leukocytosis with lymphocytosis, monocytosis and eosinophilia was rapidly followed by leukopenia and lymphocytepenia after a blood transfusion for anemia. There was a transient clinical remission, but on relapse 10 days later, quantitative and functional T cell deficiency was found together with increased IgG and IgA and with IgM values reaching 50 times greater than normal. Thymic humoral factor was successful in vitro in increasing the number of identifiable T cells (E rosetts) as well as T cell function (leukocyte migration inhibition factor production). However, the infant died suddenly, and at autopsy evidence of a generalized inflammatory reaction compatible with a viral infection was found. The thymus was small, hypoplastic and hypocellular. It is speculated that the T system deficiency may have been acquired following Epstein-Barr virus infection, and that T cell regulatory activity of immunoglobulin production was defective.

Antibodies, Viral

Cellular immunity in newborn infants and children: stimulation of lymphocyte protein synthesis as a measure of immune competence.

An assay based on the early stimulation of protein synthesis in lymphocytes has been used as an in vitro measure of cellular immune competence. 3H-labelled leucine incorporation into human peripheral lymphocytes (PBL) stimulated by the mitogens phytohaemagglutinin (PHA), wax bean agglutinin (WBA) and Concanavalin A (Con A) was measured after one day in culture. This assay offers a technical advantage over the analogous 3H-labelled thymidine incorporation assay, because of the short incubation time required and the absence of homologous serum in the assay system. Newborn infants and patients with Down's syndrome as a group had normal responses, whereas those suffering from recurrent infections demonstrated normal or hyper-reactive responses. Patients with lymphoproliferative disorders, ataxia telangiectasia, and some patients under steroid therapy had diminished immune proliferative reactions. These results are in agreement with most previously reported studies using other assay systems.

Adolescent

Leucocyte migration inhibition factor (LIF) production by lymphocytes of normal children, newborns, and children with immune deficiency.

The reproducibility of a simplified, sensitive and rapid agarose-cell droplet assay for leucocyte migration inhibition factor (LIF) activity was studied. Removal of T cells with anti-T-cell serum eliminated LIF activity, indicating that in humans it is probably the T cell that produces LIF. Cord blood lymphocytes produce LIF, although spontaneous migration of leucocytes is less than in older children. The cause of this apparently does not reside in the PMN leucocytes. Studies of children with immunodeficiency suggest that the T-cell population in humans is heterogenous. B-cell deficiencies such as hypogammaglobulinaemia, have normal PPD and PHA induced LIF production, whilst some patients with ataxia-telangiectasia have defective PPD LIF activity, their PHA LIF activity being only minimally depressed. On the other hand, Down's syndrome patients with reduced blood T cells have remarkably deficient LIF activity to PHA and relatively good activity to PPD. Children receiving steroid therapy lose much of their ability to produce LIF to the specific antigen PPD, but not to the non-specific mitogen PHA.

Adolescent

Heteroimmunization to the capsular polysaccharide of Haemophilus influenzae type b induced by enteric cross-reacting bacteria.

Cross-reacting Escherichia coli strains Easter and 89 and Bacillus pumilis fed to newborn rabbits and E. coli fed to adult rhesus monkeys did not exert untoward reactions. The E. coli regularly colonized the newborns' intestinal tract from 1 to 7 weeks. High doses of E. coli were necessary to colonize adult primates. Colonization occurred in fewer newborn rabbits and lasted only 1 to 3 weeks with B. pumilis. Colonized newborn rabbits and adult rhesus had an active Haemophilus influenzae type b (HITB) immune response. In the rabbit, colonization resulted in accelerated induction of immunoglobulin (Ig) M-. IgA-, and IgG-producing cells in the spleen, mesenteric lymph nodes, and Peyer's patches after HITB challenge. E. coli-fed and control newborn primates were naturally colonized with nasopharyngeal and enteric cross-reacting bacteria and both groups rapidly developed HITB antibodies in the absence of the homologous organisms. Human newborn stool cultures, taken at the time of discharge from the nursery, showed a 0.9% carriage rate for cross-reacting E. coli. These "carrier" infants acquired HITB antibodies more rapidly than their age-matched "noncarrier" controls.

Animals

Induction of Haemophilus influenzae type b capsular antibody in neonatal rabbits by gastrointestinal colonization with cross-reacting Escherichia coli.

In two separate experiments, newborn rabbits were fed a live suspension of either of two Escherichia coli strains which possess a "K" antigen cross-reactive with the capsular polysaccharide of Haemophilus influenzae type b. Both feedings were harmless and resulted in fecal excretion of the fed E. coli in most animals as well as active immunization of fed animals toward H. influenzae type b. Feeding non-enteropathogenic, cross-reacting E coli to newborns may be a method for inducing active immunity toward H. influenzae type b diseases by accelerating the acquisition of "natural" immunity.

Animals

Enteric bacteria cross-reactive with Neisseria meningitidis groups A and C and Diplococcus pneumoniae types I and 3.

Enteric bacteria of 1,335 individual strains were studied for serological cross-reactions with Neisseria meningitidis groups A and C and Diplococcus pneumoniae types I and III. Enterobacterial antigens cross-reactive with the capsular polysaccharides of these four bacteria were found. Bacteria cross-reactive with noncapsular antigens of meningococci and pneumococci were also observed. Since some enteric bacteria possess antigens with serological specificities similar to those of meningococci, the possibility that enteric bacteria cross-reactive with meningococcal antigens provide an antigenic stimulus for the observed age-related "natural" immunity to this pathogen is discussed.

Animals