Immune complexes in ulcerative colitis and Crohn's disease.

Sera from 156 patients with ulcerative colitis and Crohn's disease were tested for the presence of immune complexes, by the detection of anti-complementary activity and 125I-labelled Clq precipitation. Using aggregated IgG, a comparison between the two tests indicated that the anti-complementary test was most sensitive to aggregates of 11S in size, while the 125I-labelled Clq test detected aggregates over 20S in size. Excess anti-complementary activity was common in patients with active bowel disease, and in those with extra-intestinal manifestations, particularly acute arthritis, ankylosing spondylitis and liver disease. Large complexes were only common in patients with liver disease. Immune complexes in the gut mucosa may play a role in the pathogenesis of these diseases, and the deposition of circulatory immune complexes may explain at least some of the extra-intestinal manifestations.     

The replication of type A influenza viruses in the infant rat: a marker for virus attenuation

Twenty recombinant influenza virus strains bearing HSw1N1, H1N1 or H3N2 surface antigens, together with their respective wild-type or laboratory-propagated parent viruses, were inoculated into 2 day-old infant rats and their replication in the turbinates and lungs of these animals observed over a period of 5 days. In addition, the ability of each of the recombinant and parent viruses to enhance a subsequent infection of these infant rats by Haemophilus influenzae type b was determined. The results showed that both parent and recombinant viruses replicated less well in the lungs than in the turbinates of infant rats, but the titres in both tissues were generally lower for the recombinant strains. The capacity of the majority of the recombinant influenza viruses to promote bacterial infection of the infant rats, as determined by the incidence of H. influenzae bacteraemia and meningitis, was also markedly less than that of their parent viruses. A correlation between virulence for man and both the replication in infant rat turbinates and the ability to enhance H. influenzae infection, was established for the virus strains studied. The data are discussed in relationship to the value of the infant r-H influenzae system as a laboratory marker for the determination of the virulence of influenza virus strains.     

Multiple signals regulate the intracellular trafficking of HLA-DM in B-lymphoblastoid cells.

Peptide loading by major histocompatibility complex (MHC) class II molecules occurs in the endocytic pathway and is critically dependent upon the function of the class II-related molecule human leucocyte antigen-DM (HLA-DM). We have previously shown that a tyrosine-based lysosomal targeting signal present in the cytoplasmic tail of DMB has the capacity to target HLA-DM to peptide-loading compartments in HeLa cells. Here we investigate the importance of this signal in directing HLA-DM to processing compartments in professional antigen-presenting cells. We reconstituted a DMB-negative B-lymphoblastoid cell line with native or targeting-deficient DMB and show that in the absence of its tyrosine signal, DMB-Y230A is as efficient as the wild-type molecule in inducing MHC class II SDS stable dimer formation; restoring expression of the conformation-dependent DR3 epitope 16:23; the removal of CLIP; and accessing lysosomal peptide-loading compartments. By transient transfection in HeLa cells we show that Ii is able to compensate for loss of DMB-encoded targeting information. These data imply that in cells expressing physiological levels of class II, Ii and DM, there is sufficient association with Ii to direct the majority of DM into the endocytic pathway. Thus MHC class II and HLA-DM may follow similar intracellular trafficking pathways on route to antigen-processing compartments.     

Cytogenetic analysis of a mesenchymal hamartoma of the liver

Cytogenetic analysis of a mesenchymal hamartoma of the liver in a 3-year-old child revealed a balanced translocation between chromosomes 15 and 19 as the sole chromosome change.     

Transient erythroblastopenia of childhood with CD10, TdT, and cytoplasmic mu lymphocyte positivity in bone marrow.

Over three years, three children presented with anaemia, reticulocytopenia, and marrow erythroblastopenia. A pronounced lymphocytosis was also evident in two of the marrow aspirates, with increased numbers of cells bearing the immunophenotype TdT+, CD10+ HLA DR+, and cytoplasmic mu +, and reported to be compatible with acute lymphoblastic leukaemia (ALL). The clinical course of the illness was fully compatible with transient erythroblastopenia of childhood (TEC), and all three children remained well one to four years after initial presentation. It is concluded that increased numbers of lymphoid cells with a common or pre-B ALL phenotype may be found in bone marrow aspirates of children with TEC, and should not be misdiagnosed as acute leukaemia.     

A contribution of cellular immunity to protection against influenza in man

The degree of lymphocyte transformations and leukocyte migration inhibition (LMI) in the presence of inactivated A/Scotland/74 (H3N2) influenza virus vaccine was measured in blood samples collected from 56 medical student volunteers. At the same time the volunteers were skin tested, using the same vaccine. Using the antigenically similar WRL 105 (H3N2), recombinant influenza virus, the level of haemagglutination-inhibiting (HI) antibodies in serum, and neutralizing antibodies in nasal washings collected from the volunteers, were also determined. Each volunteer was then inoculated with live, attenuated WRL 105 influenza virus vaccine and infections demonstrated by virus isolations and serology.Correlations between the ability to infect the volunteers and the various parameters of humoral and cellular immunity were then determined. The results showed a good correlation between the level of serum HI antibody and infection. Thus 16 of 20 volunteers with serum HI antibody titres of 110, but only 6 of 20 volunteers with antibody levels of 130, showed evidence of infection. No direct correlation was observed between any of the other parameters measured and infection by WRL 105 virus. However, when the LMI and serum HI antibody levels were considered together, a contribution of cellular immunity, as measured by the LMI test, could be found. Of 19 volunteers with low serum HI antibody and low LMI levels, 16 were infected, whereas of 13 volunteers with low HI antibody, but with high LMI levels, only 6 showed evidence of infection with WRL 105 influenza virus.     

Lymphocyte transformation responses to phytohaemagglutinin and pokeweed mitogen in patients at differing stages of HIV infection: are they worth measuring?

AIMS--To determine whether the routine measurement of lymphocyte transformation responses to mitogenic stimuli provide any information additional to that available from routine T cell CD4 and CD8 analysis in patients with HIV infection. METHODS--The case records of 197 immunologically investigated HIV seropositive patients were reviewed. The influence of disease stage on T lymphocyte subsets and lymphocyte transformation responses (LyTR) to phytohaemagglutinin (PHA) and Pokeweed mitogen was assessed. RESULTS--The median CD3 and CD4 counts and LyTR to PHA and Pokeweed mitogen were highest in patients with persistent generalised lymphadenopathy (PGL) and decreased progressively in the order: asymptomatic patients, those with ARC, those with AIDS. LyTR to PHA was preserved in over 70% of all patients, but the response to Pokeweed mitogen was depressed in 8% of patients with PGL, 34% of asymptomatic patients, 68% of those with ARC and 78% of those with AIDS. Subnormal values of both CD4 + T cells and LyTR to Pokeweed mitogen were more common in patients with ARC and AIDS (68%) than in those who were asymptomatic or had PGL (20%). CONCLUSIONS--CD4 T cell analysis and LyTR to Pokeweed mitogen, but not to PHA, both correlate with disease states in patients with HIV infection.     

Synaptic functions in rat sympathetic neurons in microcultures. IV. Nonadrenergic excitation of cardiac myocytes and the variety of multiple-transmitter states

In the first 3 papers of this series (Furshpan et al., 1986a, b; Potter et al., 1986), a sensitive microculture procedure was used to show that sympathetic principal neurons, dissociated from newborn or adult superior cervical ganglia and grown singly on cardiac myocytes, display adrenergic, cholinergic, and purinergic functions, sometimes in isolation but more often in combination. In this paper we describe additional effects on cardiac myocytes evoked by these neurons; the effects were excitatory and insensitive to adrenergic blocking agents (and to agents that block the inhibitory effects of acetylcholine and purines). In some of these microcultures, evidence consistent with secretion of serotonin was obtained; the nonadrenergic excitatory effect was diminished or abolished by serotonin blockers or reserpine. Further evidence for serotonergic transmission is presented in the accompanying paper by Sah and Matsumoto (1987). In other cases, an as-yet-unidentified agent "X" also produced a nonadrenergic excitation. The X effect characteristically required a prolonged train of neuronal impulses, had a time course of 50-200 sec, and was insensitive to agents that affected the other transmitters, including serotonin. In addition, we discuss 2 remarkable features of the transmitter repertoire of the microcultured sympathetic neurons: expression of the several transmitters in a variety of combinations, including at-least-quadruple function, and expression of the transmitters within a particular combination in varying relative strengths. The result is a diversity of transmitter release greater than that previously reported for vertebrate or invertebrate neurons.     

Neurochemical and neuroendocrine dysregulation in affective disorders

Depressed patients demonstrate dysregulation in multiple neurochemical and neuroendocrine systems. The observed abnormalities are often subtle, involving "inefficiencies" in stress-responsive systems. Norepinephrine, acetylcholine, the hypothalamic-pituitary-adrenal axis, and the hypothalamic-pituitary-thyroid axis are among the major biochemical and hormonal sites of dysregulation in depression.