Human monoclonal antibody against a gag-coded protein of human immunodeficiency virus produced by a stable EBV-transformed cell clone.

An EBV-transformed lymphoblastoid B cell clone (A12) derived from peripheral blood lymphocytes of an HIV-1-infected individual is described. The immunoglobulin isotype produced by this clone was IgM, and Southern blot analysis of immunoglobulin gene rearrangement showed a monoclonal pattern. The A12 monoclonal antibody was specific for the p24 product of the HIV-1 gag gene.

Central nervous system involvement in HIV infection.

Central nervous system (CNS) involvement occurs frequently in patients with the acquired immunodeficiency syndrome (AIDS), but at present only a few reports have addressed the analysis of intrathecal IgG synthesis in human immunodeficiency virus (HIV)-seropositive patients with no signs of HIV-related neurologic syndromes. In this study, intrathecal IgG synthesis was investigated using several techniques in patients with different stages of HIV infection and then correlated with the state of the blood-brain barrier. Almost all patients had specific anti-HIV IgG synthesis within the CNS, suggesting the presence of HIV in the brain.

Cerebrospinal fluid lymphocytes from HIV-infected patients synthesize HIV-specific antibody in vitro.

Cerebrospinal fluid lymphocytes from six human immunodeficiency virus (HIV)-infected and three seronegative patients were studied for in vitro synthesis of HIV-specific antibody by means of Western blot analysis of lymphocyte culture supernatants. All the HIV-positive subjects showed in vitro production of HIV-specific IgG, regardless of neurological involvement, while no specific antibody synthesis was detected in seronegative individuals. These data provide the first direct evidence that HIV-specific antibody in cerebrospinal fluid is due to intrathecal synthesis.

In-vitro production of HIV-specific antibody in children at risk of AIDS.

To improve on the early diagnosis of human immunodeficiency virus (HIV) infection, 37 children born to HIV-infected mothers and 22 controls were investigated for in-vitro synthesis of IgG antibody directed against HIV components. For 14 of 16 infected children western blot showed HIV-specific IgG in the supernatants of cultures of their peripheral blood lymphocyte cultures. HIV-specific IgG synthesis was detected in cultures from 4 out of 17 seropositive children aged under 15 months with no clinical or laboratory evidence of infection.

Continuous-wave Doppler of vertebral arteries in noninvasive diagnosis and management of vertebro-basilar TIAs.

Continuous-wave Doppler and angiography of the vertebro-basilar system were used in 38 patients with vertebro-basilar transient ischemic attacks. 63 vertebral arteries were studied. Among 47 normal Doppler parameters, 46 were confirmed by angiography.

2,5-Hexanedione-induced accumulations of neurofilament-immunoreactive material throughout the rat autonomic nervous system.

In rats intoxicated with 2,5-hexanedione, nerve fibres supplying virtually all visceral organs showed large numbers of densely immunoreactive accumulations of neurofilament-like material, of fusiform, elongated, smoothly tapering morphology. In the gut, round to oval, morphologically different lesions were also present, and abnormal neurofilament-immunoreactive accumulations were revealed in oesophageal terminal end-plates. An extensive damage to autonomic nerve fibres, which are largely non-myelinated, was thus revealed in 2,5-hexanedione intoxication.

Spontaneous in vitro production of virus-specific antibody by lymphocytes from HIV-infected subjects.

In vitro synthesis of IgG directed against HIV components was detected by ELISA and Western blot assay of lymphocyte culture supernatants. Lymphocytes from HIV-infected individuals spontaneously produced antibody against HIV proteins very early in culture, suggesting in vivo activation of HIV-specific antibody-forming cells. The frequency of circulating B cells spontaneously secreting HIV-specific IgG was very high in some cases, but spontaneous HIV-specific antibody synthesis was not accompanied by polyclonal reactivation of B-cell clones of different specificity.

HIV-mediated immunodepression: in vitro inhibition of T-lymphocyte proliferative response by ultraviolet-inactivated virus.

In order to assess whether the human retrovirus HIV, like other animal retroviruses, is endowed with intrinsic immunosuppressive activity, we studied the effects of noninfectious, uv-irradiated virus on in vitro lymphocyte function. uvHIV preparations inhibited T-cell proliferation to mitogens and alloantigens, as well as mitogen-driven IL-2 production. The inhibitory effect, which was not exerted by uv-irradiated HTLV-I, was apparently not due to a decrease in cell viability and was likely associated with thermoresistant viral component(s).

Study of some early immunological parameters in aging humans.

We studied the correlation between the in vitro lymphocyte proliferative response and some early parameters of lymphocyte activation in aged people. While a consistent number of elderly subjects showed significantly decreased proliferative responses to mitogen stimulation, interleukin-1 (IL-1) production and IL-2 receptor/DR antigen expression were comparable to those of young controls. The reduction in IL-2 production observed in some aged donors did not correlate with the decreased proliferative activity in response to mitogen.

Hemodialysis leukopenia and complement function with different dialyzers.

The relationship between leukopenia and the complement system during hemodialysis was re-examined by studying not only the in vivo effects of four different dialyzer membranes (cellulose hydrate, cuprophan, cellulose acetate, and polyacrilonitrile) on leukocyte counts and complement levels, but especially by investigating the effects of these membranes on complement function in vitro. Whereas from in vivo studies no definite conclusions could be drawn, in vitro investigations provided clear-cut information. When more sophisticated technical approaches were undertaken, it became evident that hemodialysis leukopenia has to be thought of in terms of chemotactic factor generation.

Hyperproduction of IgE and T-cell dysfunction in Hodgkin's disease.

Serum IgE levels were evaluated in 119 untreated and 112 treated patients with Hodgkin's disease (HD). 38 of the nonatopic untreated patients showed significantly increased (> 300 IU/ml) IgE concentrations. No relationship could be found between increased IgE levels and depressed lymphocyte response to phytohemagglutinin (PHA) or the imbalance of TM and TG lymphocyte subsets.

Different mitogenic activity of soluble and insoluble staphylococcal protein A (SPA).

The response to SPA and Staphylococcus strain Cowan I (StaCw) of highly purified populations of peripheral blood and tonsil human lymphocytes was investigated. Purified T lymphocytes isolated from perpheral blood by E-rosetting were unable to respond in vitro to StaCw. Highly purified B-cell populations from tonsils did not show any proliferative response in the presence of soluble SPA.

Receptors for IgM: a feature of subpopulations of both T and B human lymphocytes.

Receptors for IgM were detected on peripheral blood and tonsil human lymphocytes by a rosette technique with ox red blood cells (ORBC) coated with anti-ORBC rabbit IgM. It was found that the receptors are very sensitive to handling procedures of cells and to low temperatures. An overnight incubation period at 37 degrees C was the optimal condition for the maximum expression of receptors for IgM, but the use of IgM-free media in these cultures was neither an essential nor favourable factor for an optimal rosette formation, when ORBC heavily coated with rabbit IgM were used.

Altered proportion of T mu-and T gamma-cell subpopulations in patients with Hodgkin's disease.

The ability of peripheral blood lymphocytes from patients with Hodgkin's disease (HD) to form rosettes with ox red blood cells (ORBC) sensitized by anti-ORBC purified rabbit IgM and IgG was investigated. The mean percentage of cells capable of forming rosettes with ORBC coated with IgM (EAIgM-RFC) in the peripheral blood of either untreated or X-ray-treated patients with HD was significantly lower than that of normal individuals. In the same groups of patients with HD the mean percentage of T lymphocytes equipped with receptor for IgG (T gamma lymphocytes), evaluated by a mixed fluorescent rosette assay, was significantly higher than in normal controls.

Co-operation between T and B lymphocytes from human tonsils in the response to mitogens and antigens.

Purified B lymphocytes obtained from human tonsil cell populations by removing E rosette-forming cells by density sedimentation did not proliferate at three days in response to PHA and Con A, but showed a significant 3H-labelled thymidine incorporation when the PHA response was assessed at day 6 of culture. The 6th-day responses, which was completely abolished by the reduction of T-cell contamination to less than 0-1% by re-rosetting and a second separation, was due in part to a direct activation by PHA of contaminating T cells and in part to a T cell-mediated B-cell response. When purified B cells were stimulated for 3 days by PHA in the presence of an equal number of autologous or homologous mitomycin-treated T lymphocytes a highly significant uptake of 3H-labelled thymidine was demonstrated.

In vitro lymphocyte response to the phytomitogens in untreated and treated patients with Hodgkin's disease.

In vitro lymphocyte response to phytohemagglutinins (PHA), concavalin A (Con A), and pokeweed mitogen (PW) was evaluated in untreated and treated patients with Hodgkin's disease (HD). The responding capacity to PHA was depressed, though not constantly, in the untreated patients compared with the response to lymphocytes from normal individuals. The depression was more evident, at group level, when the cells were stimulated with suboptimal concentrations of PHA.

Studies on allergens of Dermatophagoides pteronyssinus by direct and indirect RAST.

Dermatophagoides pteronyssinus (DP) extract was fractionated by Sephadex G-75 and liquid isoelectric focusing (IEF) and the allergenic activity of different fractions was monitored by direct and indirect RAST. The fractionation on Sephadex G-75 showed that the allergenic activity of DP extract was related to wide molecular weight spectrum components, even though the maximum amount was recovered in effluent that contained protein with a molecular weight ranging between 25,000 and 12,500 daltons. By fractionation of the mite extract on IEF, three main peaks of allergenic activity (pI less than 3.

[Immunological aspects of bronchial asthma].

Advances in understanding of bronchial asthma are to be expected from more detailed information on the immuno-pathological mechanisms involved. Reaginic IgE antibodies are responsible for the great majority of extrinsic asthma, but in some cases immune complexes could probably be also important. A great progress has been achieved after reproducible methods for detecting cellular and serum specific IgE antibodies were introduced.