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Biomedical subjects

H D Foss

Publications and source records attributed to H D Foss.

At least 73 records · Page 4Linked to original sources
PubMed1997

Molecular biology of Hodgkin's disease.

The mist surrounding the origin and genesis of HRS cells of classical HD is beginning to dissipate. Molecular biological studies of classical HD at the single cell level strongly suggest that the HRS cells in the majority of cases represent a monoclonal outgrowth of late germinal centre B cells that have lost their capacity to express IG through crippling mutations introduced during the germinal centre reaction. Because of the expression of T cell antigens and/or cytotoxic molecules, the HRS cells of a minority of classical HD cases appear to originate from T cells. Under physiological conditions, B cells that are unable to express IG are eliminated by apoptosis. In most B cell derived classical HD cases, the HRS cells have lost their IG gene coding capacity through mutation and should therefore die of apoptosis. Since this usually does not happen, blockade of the apoptotic pathway may be a major event in the pathogenesis of B cell related classical HD. It is tempting to assume that viruses such as EBV, as well as regulator genes that normally monitor the human genome for damaged DNA, such as TP53, might be involved in the postulated hindrance of the apoptotic pathway, leading to the genesis of classical HRS cells.

Chromosome Aberrations↗
PubMed1996

Anaplastic large-cell lymphomas of T-cell and null-cell phenotype express cytotoxic molecules.

To further specify the cellular origin and nature of anaplastic large-cell lymphoma (ALCL) and its relationship to other lymphoid neoplasms, particularly Hodgkin's disease (HD), we investigated the presence of cytotoxic molecules in a large well-characterized series of these tumors. For expression of the cytotoxic molecules perforin and granzyme B, in situ hybridization (ISH) and immunohistology were used, respectively. Overall, 23 of 25 ALCLs of T/null phenotype and five (three mixed cellularity and two nodular sclerosis) of 57 HD cases showed the presence of perforin transcripts and/or granzyme B molecules in neoplastic cells. Polymerase chain reaction (PCR) analysis of ALCLs showed that most (10 of 11) cases of null-cell ALCL (null-ALCL) contained a clonal rearrangement of T-cell receptor beta-chain genes, as did T-cell ALCL (T-ALCL; 9 of 10 cases). However, both cytotoxic molecules and clonally rearranged T-cell receptor beta-chain genes were absent in seven of seven and eight of nine cases of B-cell ALCL (B-ALCL), respectively. These data show that all or nearly all T-ALCLs, irrespective of the clinical subform or the lack of T-cell-associated molecules, are derived from activated cytotoxic T cells. The same appears to be true for the neoplastic cells of rare HD cases. These findings indicate that T-ALCLs are different from B-ALCLs and the majority of HD cases, and suggest that some HD cases, especially those with T-cell antigen-positive tumor cells, may be closely related to T-ALCL, at least in terms of cellular origin.

Biomarkers↗
PubMed1996

Expression of Epstein-Barr virus-gene products in Burkitt's lymphoma in Northeast Brazil.

The Epstein-Barr Virus (EBV) is consistently found in tumor cells of Burkitt's lymphoma (BL) endemic in central Africa and malaria is considered a pathogenic cofactor. In contrast, fewer than 20% of BL cases occurring in Western countries are EBV-associated. We have investigated 54 BL cases from Bahia, a tropical region of Northeast Brazil, for expression of EBV gene products by in situ hybridization and immunohistology and performed typing of the EBV by polymerase chain reaction. Ten pediatric BL cases from Germany served as controls. New cases of malaria were not observed in the period and area of our study. Small nuclear EBV encoded transcripts, EBER, were found in tumor cells of 47 of 54 Brazilian cases (87%) but in only 2 of 10 German cases (20%). Type I latency of the EBV infection with absence of EBV-encoded proteins LMP1 and EBNA2 was found in 45 of 47 of the EBER-positive Brazilian cases. In two cases, occasional LMP1-containing tumor cells were found in the neighborhood of small Schistosoma mansoni granulomas and scars. BHLF1 transcripts associated with lytic EBV infection could be detected in few cells in 3 of the 40 EBER-positive Brazilian cases investigated. EBV type A was found in the majority of Brazilian BL cases (20 of 30 A-type, 7 of 30 B-type, and 3 of 30 not amplifiable). Our results indicate that the association of Bahian BL with EBV, but not the regional prevalence of malaria, is similar to endemic African BL. In two cases, type II latency was found in association with schistosomiasis, suggesting a role of this parasitosis in the induction of an EBV expression pattern that is unusual for BL. Because chronic schistosomiasis is associated with elevated Th2 cytokine expression resulting in reduced cell-mediated cytotoxicity, it seems possible that altered local immunity is responsible for this peculiar phenotype.

Adolescent↗
PubMed1996

Frequent expression of interleukin-10 by Epstein-Barr virus-harboring tumor cells of Hodgkin's disease.

Tumor cells of Epstein-Barr virus (EBV)-associated Hodgkin's disease (HD) express the viral protein, latent infection membrane protein-1 (LMP1), but evade cytotoxic responses normally directed at this antigen. We tested whether local production of the immunoregulatory interleukins (IL)-4 and -10 may have a role in this process. IL-4 RNA was not detectable in any of the HD cases. By contrast, isotopic in situ hybridization and correlation with the presence of EBV gene products showed significantly higher proportions of cases with IL-10 expressing tumor cells in LMP1-positive (17 of 26, 66%) as compared with LMP1-negative HD cases (six of 37, 16%). Absence of EBV BCRF1 RNA indicated that the transcripts originated from the cellular IL-10 gene. Similarly, an association between IL-10 expression and EBV-infection of tumor cells was found in AIDS-related malignant non-Hodgkin lymphomas (ARL). Very small proportions of EBV-infected cells, mainly blasts, expressed IL-10 in infectious mononucleosis tonsils. Thus, although not entirely exclusive to EBV-positive cases, IL-10 expression is frequently associated with EBV-infection in HD and ARL and appears to be upregulated by EBV, most likely through LMP1. In view of the established inhibitory effects of IL-10 on cell mediated immunity, it is suggested that IL-10 expression may contribute to evasion of LMP1-positive cells from cytotoxicity directed at viral antigens.

Base Sequence↗
PubMed1996

Monokine expression in Langerhans' cell histiocytosis and sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)

Langerhans' cell histiocytosis (LCH) is a clonal proliferation of Langerhans cells (LC) showing histologically an abundant reactive infiltrate composed of macrophages and lymphocytes, as well as eosinophilic and neutrophilic granulocytes. Rosai-Dorfman disease (RDD) shows a sinusoidal accumulation of large histiocytic cells with an immunophenotype similar to LC of LCH. The histological picture of LCH is reminiscent of an inflammatory disorder and LC may produce cytokines and are influenced by these soluble factors. This study set out to establish the monokine expression pattern in LCH in comparison with those of RDD; dermatopathic lymphadenopathy, which also shows a proliferation of S100-positive dendritic cells; and LC in normal skin specimens. Isotopic in situ hybridization was used for the detection of transcripts of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 beta, in some cases combined with immunohistology for the S100 protein or CD68. In all 11 tissue samples from eight patients, LC of LCH expressed TNF-alpha; in two cases IL-1 beta transcripts were additionally noted in some LC, whereas IL-6 was found in reactive cells. Large histiocytic cells of RDD expressed all three monokines, whereas minimal or no expression of these cytokines could be detected in interdigitating reticulum cells in dermatopathic lymphadenopathy. In two out of five normal skin samples, only TNF-alpha specific signals were observed in LC. These data suggest that histologically different lesions of the histiocytic/dendritic cell system display distinct cytokine profiles. The expression of monokines, which have been demonstrated to influence various functions of epidermal LC, may play a role in the pathogenesis of LCH. Systemic symptoms in RDD may be related to enhanced production of monokines in these lesions.

Child↗
PubMed1996

Fatal Mucor pneumonia after treatment with 2-chlorodeoxyadenosine for non-Hodgkin's-lymphoma.

Fungal infections, in addition to bacterial and opportunistic infections such as Pneumocystis carinii pneumonia, may evolve in patients with infectious complications due to iatrogenic immunosuppression. Aside from common Candida and Aspergillus species, rare fungi like Mucor must be considered in patients with neutropenia or prolonged impaired T-cell function. Here we report on a patient with a low grade lymphoma who was treated with 2-chlorodeoxyadenosine because of disease progression. After recovery from Pneumocystis carinii pneumonia he presented again with clinical signs of pneumonia. No pathogen was found on bronchoscopy and he died rapidly. In the lungs a massive necrosis was seen in which nonseptated hyphae identified as Mucor species were demonstrated.

Aged↗
PubMed1996

Primary malignant melanoma of the oesophagus.

We report the case of a 74-year-old female patient in whom a primary malignant melanoma of the oesophagus was detected at the time of investigation of phlebothrombosis. Therapy of choice for this extremely rare tumour is radical surgical resection of the oesophagus. Even after surgical resection, primary oesophageal melanomas have a very poor prognosis. According to the present state of knowledge, it remains unclear to what extent the prognosis could be improved by adjuvant therapeutic procedures with radiotherapy or chemotherapy and immunostimulation.

Aged↗
PubMed1996

Inflammatory pseudotumors of lymph node origin show macrophage- derived spindle cells and lymphocyte-derived cytokine transcripts without evidence of T-cell receptor gene rearrangements. Implications for pathogenesis and classification as an idiopathic retroperitoneal fibrosis-like sclerosing immune reaction.

Sclerosing pseudotumorous immune reactions of the retroperitoneum have been shown to consist of HLA-DR-positive spindle-shaped fibroblasts and macrophages that resemble fibroblasts, and in some instances they contain clonal populations of T lymphocytes not found in granulation tissue, keloids, nodular fasciitis, or fibromatoses. In patients who are iatrogenically immunosuppressed, circulating monocytes may be induced in vitro to transform into spindle-shaped macrophages, and secrete collagen after stimulation by conditioning medium from activated T lymphocytes. The authors investigated a series of five inflammatory pseudotumors (IPT) of lymph node origin for identification of spindle-shaped macrophages, T-cell receptor gene rearrangements, and lymphocyte-derived cytokine mRNA production. All cases of IPT demonstrated spindle-shaped macrophages resembling fibroblasts or myofibroblasts characterized by vimentin, CD45 (LCA), CD68 (KP1) or HAM-56, and HLA-DR(LN3) immunoreactivity and demonstrated production of procollagen-alpha1 (I) mRNA by in situ hybridization. Clonal T-cell receptor chain gene rearrangements were undetectable by polymerase chain reaction. Strong specific lymphocyte-derived interleukin-1beta and interleukin-6 mRNA cytokine transcripts were identified. Although all patients with IPT were managed with steroids and nonsteroidal anti-inflammatory medication, some had treatment-refractory disease. Because all-trans retinoic acid has been demonstrated to inhibit the in vitro transformation of monocytes into collagen-producing spindle-shaped macrophages ("neofibroblasts"), it may be of benefit for patients with IPT.

Antigens, CD↗
PubMed1996

Interleukin-8 in Hodgkin's disease. Preferential expression by reactive cells and association with neutrophil density.

Hodgkin's disease (HD) shows rare neoplastic Hodgkin and Reed-Sternberg cells embedded in an abundant reactive infiltrate containing, among other cell types, neutrophilic granulocytes. Interleukin (IL)-8 is chemotactic for neutrophils. The expression of IL-8 was tested by in situ hybridization with 35S-labeled IL-8-specific RNA probes on 38 cases of HD. Reactive lesions, non-Hodgkin's lymphomas of B and T phenotype, and Langerhans cell histiocytosis served as controls. IL-8 expression was observed in Hodgkin and Reed-Sternberg cells in 3 of 33 cases of classical HD and in reactive cells in 20 of 33 HD cases as evidenced by combined isotopic in situ hybridization and immunohistology for the demonstration of cell-type-characteristic antigens or enzyme histochemistry for chloroacetate esterase. IL-8-positive cells were more numerous in cases of nodular sclerosing HD as compared with the mixed cellularity histotype (P = 0.01). The number of IL-8-positive cells and the density of neutrophils were positively correlated (P < 0. 01). In 5 cases of lymphocyte-predominant HD, IL-8 expression was not displayed. Non-Hodgkin's lymphoma cases contained IL-8 transcripts only in 1 of 23 cases in sparse reactive cells. In 4 of 7 cases of Langerhans cell histiocytosis, IL-8-specific signals were displayed in S100-negative cells. In conclusion, IL-8 expression in HD is largely confined to reactive cells and associated with infiltration by neutrophils. Elaboration of other cytokines by Hodgkin and Reed-Sternberg cells and reactive cells may explain the frequent expression of this cytokine in HD, particularly in the nodular sclerosing type.

Cell Count↗
PubMed1995

Patterns of cytokine gene expression in peripheral T-cell lymphoma of angioimmunoblastic lymphadenopathy type.

Peripheral T-cell lymphoma of angioimmunoblastic lymph-adenopathy type (AILD-TCL) is histologically characterized by a mixed infiltrate of atypical T cells, B cells including B immunoblasts, and plasma cells, as well as eosinophilic granulocytes accompanied by proliferated high endothelial venules, while, clinically, fever and weight loss are often observed. These morphologic and clinical pecularities are widely believed to reflect abnormal patterns of cytokine expression. To evaluate this hypothesis, 11 lymph nodes with AILD-TCL were studied for the presence of tumor necrosis factor-alpha (TNF), lymphotoxin (LT), interleukin-6 (IL-6), and IL-1 beta transcripts by in situ hybridization (ISH) using [35S]-labeled cytokine-specific RNA probes in seven cases subsequent to immunohistology for cell type characteristic antigens. Expression of all four cytokines was strongly enhanced in AILD-TCL when compared with the control groups of lymphoblastic lymphomas and peripheral T-cell lymphomas, other than AILD-TCL. TNF and LT transcripts were present in atypical T cells and in a variable proportion of B immunoblasts in all AILD-TCL cases, whereas IL-6 and IL-1 beta specific transcripts were mainly found in nonlymphoid cells. To verify a possible cytokine expression by Epstein-Barr virus (EBV)-infected cells, which are frequently present in AILD-TCL, the detection of EBV-encoded nuclear RNAs (EBER) was combined with ISH for cytokine transcripts. It became evident that expression of LT and TNF by EBV-infected cells was largely restricted to B immunoblasts, which were only infrequently present in most AILD-TCL cases, whereas the expression of IL-6 was very rare, and IL-1 beta was not found in EBV-infected cells. These data suggest that expression of TNF and LT genes may contribute to the characteristic histologic and clinical features of AILD-TCL and that cytokine expression by EBV-infected cells does not, in most cases, contribute significantly to the overall cytokine expression. Because it has been shown that LT is an autocrine growth factor for EBV-infected B cells, expression of this cytokine could contribute to the proliferation of EBV-infected B cells in AILD-TCL and, in the setting of immunosuppression, may ultimately play a role in the development of B-immunoblastic lymphomas.

Cytokines↗
PubMed1995

Frequent expression of IL-7 gene transcripts in tumor cells of classical Hodgkin's disease.

Interleukin-7 (IL-7) is a pleiotropic cytokine acting mainly on cells of the hematolymphoid system. In vitro studies have shown enhanced proliferation of acute lymphoblastic leukemia cells in response to IL-7. On the other hand, tumor cell lines transfected with a functioning IL-7 gene and subsequently transplanted into mice resulted in a prominent inflammatory infiltrate and reduced tumorigeneicity. These data suggest an important role of this cytokine in the pathophysiology of lymphoid neoplasms. Because little is known about the in vivo expression of this cytokine in various neoplastic and nonneoplastic lesions of the lymphoid system, we examined frozen and paraffin-embedded tissue samples of normal, reactive, and malignant lymphoid lesions using in situ hybridization with a 35S-labeled RNA probe specific for IL-7. Tumor cells of nodular sclerosing and mixed cellularity type of Hodgkin's disease displayed IL-7-specific signals in 24 of 31 cases. Among reactive lesions, only thymic tissue showed labeling within both cortex and medulla (4 of 7 cases), whereas in tonsils clear-cut IL-7-specific signals could not be found. Tissues infiltrated by B-type chronic lymphocytic leukemia or T- or B-type lymphoblastic lymphoma showed cytokine-specific signals in only one case of lymphoblastic lymphoma in rare reactive cells. In conjunction with the finding of elevated levels of IL-7 in the serum of many patients with Hodgkin's disease, our data suggest an important role of this cytokine in the pathogenesis of Hodgkin's disease. The prominent reactive infiltrate observed in most cases of Hodgkin's disease could be a consequence of elevated local levels of this cytokine as similar infiltrates are also observed in tumors in mice resulting from injection of tumor cell lines transfected with a functioning IL-7 gene.

Child↗
PubMed1995

CD30 antigen in embryonal carcinoma and embryogenesis and release of the soluble molecule.

The expression, serological detection, and possible functional role of the CD30 antigen in Hodgkin's disease and anaplastic large cell lymphoma is well documented. In embryonal carcinoma (EC), the expression of this cytokine receptor has been demonstrated only by immunohistology. Because the CD30 monoclonal antibody Ki-1 was found to cross-react with an unrelated molecule, we examined by in situ hybridization testicular germ cell neoplasms for the presence of CD30-specific transcripts. CD30 mRNA was detectable in the tumor cells of 9 of 9 cases of EC or mixed germ cell tumors with an EC component but in no other nonlymphoid tumors. Thus, the CD30 transcript expression pattern proved to be identical to the immunostaining pattern seen with the CD30-specific monoclonal antibody Ber-H2. By Northern blot analysis, CD30 transcripts could be demonstrated in the EC cell line Tera-2. Employing a highly sensitive second generation sandwich enzyme-linked immunosorbent assay, we could detect the soluble CD30 molecule in 8 of 8 sera from patients with a diagnosis of EC but not in 8 of 10 sera from patients with other testicular germ cell tumors. In fetal tissue, no CD30-expressing germ cells or epithelial cells could be observed. Thus, the cellularly expressed CD30 marker for testicular neoplasms of EC type. Moreover, the serum levels of soluble CD30 antigen seem to be a promising parameter for monitoring patients with EC.

Adolescent↗
PubMed1994

Patterns of cytokine gene expression in infectious mononucleosis.

Primary infection with Epstein-Barr virus (EBV) may arise as infectious mononucleosis (IM) in adolescents and young adults. Morphologically, IM-affected lymphoid tissue is characterized by expanded interfollicular areas with formation of atypical lymphoid blasts. It is assumed that morphology and clinical presentation of IM are related to characteristic patterns of cytokine production by EBV-infected and reactive cells. We studied IM tonsils of eight patients and six normal tonsils with a double in situ hybridization procedure using [35S]-labeled RNA probes specific for various cytokines and digoxigenin-labeled probes for the detection of the nuclear EBV encoded RNA transcripts, EBER 1 and 2. All of the IM cases displayed the same distinct cytokine gene expression pattern. When compared with interfollicular areas of normal tonsils, expression of lymphotoxin (LT), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 beta, but not IL-8 or IL-1 alpha was strongly enhanced in interfollicular areas in IM tonsils. LT was expressed predominantly by EBV-infected cells. TNF-alpha transcripts were also present in EBV-infected cells, although in smaller proportions. IL-6 specific signals were only found in few EBV-infected cells. IL-1 alpha-, IL-1 beta-, and IL-8-specific signals were not observed in EBV-infected cells, but were present at high signal intensity in many cells within and around foci of EBV-infected cells (IL-1 beta), next to areas of necrosis (IL-8, IL-1 beta), or in epithelial cells (IL-1 alpha). These data suggest that EBV infection in form of IM results in induction of specific sets of cytokine genes in EBV-infected and in neighboring EBV-negative cells contributing to the characteristic morphology and cellular arrangement of the lesion as well as the clinical presentation.

Cytokines↗
PubMed1994

A case of disseminated toxoplasmosis-value of PCR for the diagnosis.

Extracerebral toxoplasmosis has recently gained greater attention as a consequence of the AIDS epidemic. Serological techniques are unreliable, while isolation of the parasite is either time-consuming or insensitive. We here report a case of disseminated toxoplasmosis in a patient with AIDS. Diagnosis was suggested by serological tests and confirmed by PCR and Southern blot hybridisation or nested PCR. Detection of specific DNA was feasible in bronchoalveolar fluid, blood, serum and tissue samples. Direct detection of parasite-specific DNA by PCR and by nested PCR proved to be a promising, sensitive and rapid method for the diagnosis of disseminated toxoplasmosis, enabling us to promptly initiate specific treatment.

AIDS-Related Opportunistic Infections↗
PubMed1993

Lymphotoxin, tumour necrosis factor and interleukin-6 gene transcripts are present in Hodgkin and Reed-Sternberg cells of most Hodgkin's disease cases.

Tissue specimens from 26 cases of Hodgkin's disease (HD) and six HD-derived cell lines were analysed for tumour necrosis factor (TNF), lymphotoxin (LT), and interleukin (IL)-6 RNA transcripts by in situ hybridization, in some cases subsequent to immunohistology for CD30 antigen. LT and TNF transcripts were found in tumour cells of all cases; IL-6 gene transcripts were detectable in 19/23 cases. Presence of RNA specific for these cytokines was not correlated with any of the following parameters: sex, symptoms and histotype, as well as immunophenotype and association of the tumour cells with Epstein-Barr virus. Rather, the presence of LT, TNF and IL-6 transcripts appeared to characterize Hodgkin and Reed-Sternberg cells in general, supporting concepts which suggest that HD represents a malignancy of cytokine secreting activated cells, and that many of the features distinguishing HD from other malignant lymphomas may ultimately be due to expression of cytokines. LT and TNF RNA transcripts were also found in five HD-derived cell lines, whereas supernatants of these cell lines contained high levels of LT, but low or undetectable levels of TNF activity. This suggests that, although not detectable at the level of RNA transcripts, differences between HD cases may exist on the level of cytokine gene transcript processing, translation and polypeptide secretion.

Adolescent↗
PubMed1992

Follicular dendritic cells are a major reservoir for human immunodeficiency virus type 1 in lymphoid tissues facilitating infection of CD4+ T-helper cells.

Human immunodeficiency virus type 1 (HIV-1) infection causes progressive depletion of CD4/HIV-receptor-positive T helper lymphocytes, ultimately leading to AIDS. The major HIV reservoir and site of T-helper cell infection in lymphoid tissues, however, has remained poorly defined. The authors used in situ hybridization in combination with immunohistologic labeling techniques to identify the phenotype of HIV-infected cells in lymph nodes from patients at different stages of HIV-infection. The number of HIV-infected macrophages, widely considered the major site of HIV replication, was extremely low. There was no evidence for HIV-infection of endothelial and interdigitating reticulum cells. However, HIV RNA was found in small but consistent proportions of CD45RO-positive T cells and in the vast majority of follicular dendritic cells (FDC) in a pattern suggestive of active infection in addition to HIV-immunocomplex trapping on cell membranes. FDC may therefore be a major HIV reservoir and since T-helper cells travel through the FDC meshwork during their migration within lymphoreticular tissues, it appears likely that HIV-replicating T cells may infect FDC, which then infect new T cells, thus causing a gradual dissemination of the virus to all FDC and thereby a steadily increasing infection of T-helper/memory cells within germinal centers. This results in CD4+ T cell depletion, and ultimately, in immunodeficiency.

Adult↗
PubMed1991

[Lymphoid tissues and AIDS: role of lymphocytes and follicular dendritic cells (FDC)].

Currently discussed models of AIDS pathogenesis attribute a pivotal role to HIV-variants developing in T cells during the course of the disease resulting in an increasingly rapid depletion of the infected T cells. Such models do not however explain the morphological findings observed in AIDS lymphadenopathy. To clarify the significance of the hyperplasia and subsequent destruction of the lymphoid follicles in HIV-related lymphadenopathy, we used in situ hybridization in combination with immunohistological labelling techniques to identify the phenotype of HIV-infected cells in lymph nodes. In addition to few T helper cells, mainly in germinal centres, large amounts of HIV-RNA were found in CD4-negative follicular dendritic cells (FDC) rather than in macrophages or other cells. This finding is well in accordance with the recent observations made by other authors suggesting that purified FDC can be infected with HIV in vitro. Furthermore, TNF alpha expression is localized mainly in centroblasts (activated B cells) of germinal centres. TNF alpha, released by antigen-activated B cells in vitro, has been shown to induce HIV replication in latently infected T cells. On the basis of these observations we propose that latently infected CD4+ T cells, having entered germinal centres, start HIV replication under the influence of cytokines present in this microcompartment of all lymphoreticular tissues. Here the T cells infect FDC which, in turn, pass on the virus to new healthy T helper cells. This model may explain both peculiarities of the lymphadenopathy syndrome as well as the long latency period of HIV-infection, ultimately leading to AIDS.

Acquired Immunodeficiency Syndrome↗