Judit Szelényi

HIV transmission from female to male at improperly protected sexual intercourse

There is growing evidence that human immunodeficiency virus (HIV) infection can be transmitted from female to male after only 2 sexual contacts. The authors present a case in which the wife was infected with HIV in March 1986 as a result of transfusion of blood from a homosexual. She tested positive for HIV in January 1987 and in February was notified of her positive test result. The couple had had regular unprotected sexual intercourse between April 1986 and February 1987. In February 1987 the patients husband was negative for HIV infection and condom use was initiated. By October 1987 the husband was found to be seropositive for HIV. The couple reported that the condom had torn on several occasions since protected intercourse was initiated. It cannot be determined whether HIV was transmitted before February during unprotected intercourse and the husband seroconverted after the 1st blood sampling or whether HIV was transmitted after notification of the wifes seropositive status.

Intact noradrenaline transporter is needed for the sympathetic fine-tuning of cytokine balance.

Earlier studies demonstrated that cytokine production is under the tonic control of noradrenaline. As the level and/or the duration of noradrenaline action is regulated by the noradrenaline transporter (NET), which is also a target of antidepressant treatment, we studied its role in the regulation of the cytokine response during inflammation. The endotoxin-evoked tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 response was studied in genetically produced noradrenaline transporter-deficient (NET-KO) mice and by treatment with desipramine, a monoamine uptake-blocker antidepressant. NET-KO mice responded to endotoxin with significantly lower TNF-alpha and interleukin-10 production in comparison to their wild-type counterparts. Functional involvement of both alpha- and beta-adrenoceptors could be demonstrated in our model systems, using 7,8-methylenedioxy-14 alpha-hydroxy-alloberbane.HCl (CH-38083) and propranolol; however, the differences between the two phenotypes remained, suggesting a limited role of alpha-adrenoceptors in the observed changes. Acute treatment of both wild-type and NET-KO mice with desipramine significantly decreased the TNF-alpha response and significantly increased interleukin-10 production, indicating the role of an intact noradrenaline transporter in anti-inflammatory responses.

The inducibility of TNF-α production is different in the granulocytic and monocytic differentiated forms of wild type and CGD-mutant PLB-985 cells

Chronic granulomatous disease is an inherited disorder associated with a defect in phagocytic cell oxidative metabolism resulting in ineffective microbicidal activity. Consequently, patients with chronic granulomatous disease suffer from recurrent infections. Published data show that besides the failure to produce superoxide and its derivatives, other functional problems can also be found in chronic granulomatous disease‐mutant cells. Since in innate immune responses other mediators, such as cytokines, also play an important role, we hypothesized that there may be a disturbance in cytokine production by chronic granulomatous disease‐mutant cells as well. To prove this hypothesis, the production of tumour necrosis factor‐alpha, an important proinflammatory cytokine, was determined by enzyme‐linked immunosorbent assay in wild‐type and chronic granulomatous disease‐mutant myelomonoblastic PLB‐985 cells in their immature, granulocytic and monocytic/macrophage differentiated forms. Tumour necrosis factor‐alpha production was induced with N‐formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine (100 nmol/L), lipopolysaccharide (10 µg/mL), opsonized zymosan (100 µg/mL) or phorbol 12‐myristate 13‐acetate (100 nmol/L) for 24 h. We could demonstrate that: (i) there were marked differences in tumour necrosis factor‐alpha production only in the differentiated forms of both wild‐type and chronic granulomatous disease‐mutant cells, while there were no differences in the case of their immature counterparts; (ii) only chronic granulomatous disease‐mutant cells retained sensitivity to phorbol 12‐myristate 13‐acetate both in their granulocytic and monocytic forms, although phorbol 12‐myristate 13‐acetate responsiveness was a characteristic of both types of immature cells; (iii) the granulocytic form of wild‐type cells produced tumour necrosis factor‐alpha after opsonized zymosan stimulation, but such a response was not observed in cells originating from the chronic granulomatous disease‐mutant cell line; (iv) with the monocytic forms, significantly higher tumour necrosis factor‐alpha production could be induced by lipopolysaccharide in the wild‐type cells than in the chronic granulomatous disease‐mutant cells, although there was no difference in their lipopolysaccharide receptor CD14 expression. In summary, these data show an altered inducibility of tumour necrosis factor‐alpha production by chronic granulomatous disease‐mutant cells. Our observations suggest a further defect in differentiated chronic granulomatous disease‐mutant cells in addition to the known defect in reduced nicotinamide adenine dinucleotide phosphate oxidase, which may contribute to the development of susceptibility to infections in people with chronic granulomatous disease.

Platelet-Activating Factor Evokes Ca2+ Transients After the Blockade of Ryanodine Receptor by Dantrolene in RAW 264.7 Macrophages

In the present study we studied platelet-activating factor (PAF)-, and ATP-induced increases in intracellular Ca2+ concentration ([Ca2+]i) using RAW 264.7 macrophages filled with fura-2/AM and imaged with fluorescence video microscopy. We found that the prevalence of detectable [Ca2+]i responses to PAF application was significantly higher in the presence of dantrolene. Dantrolene itself significantly decreased basal [Ca2+]i of macrophages compared to control cases after a 20-min incubation period. In the dantrolene-treated cells even the peak [Ca2+]i in response to PAF (as an average of all cells) was below the baseline of control suggesting that decreased [Ca2+]i plays a permissive role in the Ca2+ rise induced by PAF in macrophages. In contrast to the effect of PAF, neither the amplitude of response to ATP nor the frequency of responding cells changed significantly during dantrolene treatment in our experiments. These cells were able to respond to a standard immune stimulus as well: lipopolysaccharide (LPS) was able to increase [Ca2+]i. Our data indicate that the effectiveness of PAF to increase [Ca2+]i in RAW 264.7 macrophages depends on the resting [Ca2+]i. It has also been shown in this study that PAF and ATP differently regulate Ca2+ homeostasis in macrophages during inflammatory response and therefore they possibly differently modulate cytokine production by macrophages.

The polymorphic human TLX-B/CD46/MCP system and its implications in transplantation and reproduction

TLX antigens have been found on most peripheral blood cells, trophoblasts, seminal vesicle cells and sperms. These antigens seem to be associated with the membrane co‐factor protein (MCP) and the CD46 antigen. Alloantibodies to TLX antigens with FctRII‐blocking features were obtained by transfusion of leucocytes or platelets. Preliminary population studies revealed that alloantibodies to TLX/CD46/MCP recognize four overlapping specificities. The terminology TLX‐B was introduced with specificities TLX‐BI, B2, B3, B4 and frequencies obtained in the population were: 38%, 46%, 42% and 26%, respectively. Family studies showed an independent segregation of the TLX and HLA alleles.

Temporary Tolerance or Suppressive Regulation Induced By Non MHC Alloantigens in Transplantation and Pregnancy

A special type of tolerance or suppressive regulation will be reported, which can be characterized by the complementary participation of two alloantigen systems; the major histocompatibility complex, and either a minor histocompatibility or certain type of differentiation antigen (secondary, subordinated) alloantigen system of functional importance. There are representative experimental observations on this phenomena, from which one characteristic model, reported by Hutchinson and Morris (Hutchinson and Morris 1987) is explained. Prior to kidney transplantation between RTL incompatible rats recipients were transfused with blood obtained from various strains characterized by either matching or mismatching with the transfusion and organ donor or recipient strain in the minor histocompatibility system. The matching between transfusion and kidney donor and a mismatching between transfusion donor and organ recipient as regards minor histocompatibility alloantigen system has to be emphasized as a new requirement. No similar situation has been reported in human beings. However, the induction of tolerance by transfusion in certain models is a well established phenomena. The importance of class II antigen matching between transfusion donor and recipient were outlined and proved in series of clinical observations based on in vivo and in vitro parameters including cytotoxic antibody production, MLC, cytotoxic precursor cell function and kidney survival (Lagaay et al. 1989, Claas et al 1991, van Rood and Claas 1990, de Waal and van Twuyer 1991).

Results of longitudinal immunological surveillance of individuals directly or indirectly infected by a single HIV seropositive donor

Abstract Before the introduction of obligatory blood donor screening for HIV-antibodies in Hungary (July 1, 1986) a male homosexual blood donor infected three recipients; two of them in turn infected their spouses. The donor exhibited no HIV-associated symptoms and his permanent homosexual partner remained seronegative and PCR negative. By contrast, two of the three recipients died of AIDS and in longitudinal immunological surveillance the immune parameters of the recipients and even their spouses was found to be much worse than that of the donor. These findings suggest that a marked increase in the pathogenicity of the donors HIV strain(s) or a selection of a virulent strain occurred upon transfusion of his blood and this HIV strain was heterosexually transmitted by the recipients to their spouses. Another less probable explanation could be the presence of a yet unknown mechanism in the donor which repressed virus replication.