Plasma fibronectin values in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex

The authors studied the circulating fibronectin concentrations in the plasma of 24 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) and of 74 age- and sex-matched healthy blood donors. They adapted a commercially available turbidimetric immunoassay for use with a centrifugal analyzer. The assay showed within-run precision of 2.1%, 2.3%, 1.8%, and 1.1%, and an accuracy of 90%, 99%, 98%, and 98% at fibronectin concentrations of 126 mg/L, 200 mg/L, 293 mg/L, and 317 mg/L, respectively. Between-run precision was 5%, 3%, and 2% for 66 mg/L, 218 mg/L, and 283 mg/L concentrations, respectively. Plasma fibronectin values obtained from the healthy blood donors were in good agreement with those values reported by other investigators using various methods. No significant differences between the plasma fibronectin values of the patient population (mean +/- 2 SD = 294 mg/L +/- 110 mg/L) and of the control group (mean +/- 2 SD = 311 mg/L +/- 130 mg/L) were noted. The authors conclude that the measurement of fibronectin concentrations in patients with AIDS or ARC does not contribute significantly to the diagnosis and therapeutic management of these patients.     

Specificity of anti-lymphocyte antibodies in sera from patients with AIDS-related complex (ARC) and healthy homosexuals.

The presence and specificity of anti-lymphocyte antibodies (ALA) was investigated in sera from male homosexuals with AIDS-Related Complex (ARC) as well as healthy homosexuals. Individuals in the healthy homosexual group had no detectable antibodies to human immunodeficiency virus (HIV). Antibodies reactive with normal peripheral blood mononuclear cells were detected by Western blot analysis in sera from both groups of homosexuals. Of those individuals whose sera contained ALA, 71% of ARC patients and 83% of healthy homosexuals had antibodies recognizing a 73 kilodalton (kD) molecule. ALA present in ARC sera reacted with CD3+, CD4+ and CD8+ lymphocytes while little reactivity with B cells was observed. Our results indicate that ALA appear in homosexuals prior to HIV infection and are reactive primarily with T lymphocytes. A 73 kD structure associated with the T cell membrane is frequently the target for these antibodies.     

Neuropsychological outcome of zidovudine (AZT) treatment of patients with AIDS and AIDS-related complex

Two hundred eighty-one patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex were enrolled in a double-blind, placebo-controlled trial of the efficacy and safety of orally administered zidovudine (azidothymidine or AZT). Significant clinical benefits and adverse experiences have been reported from this trial. Because neuropsychiatric dysfunction is often associated with human immunodeficiency virus (HIV) infection, a brief affective and neuropsychological examination was administered over 16 weeks of the trial to evaluate any changes in neuropsychological function that occurred with drug administration. Patients receiving zidovudine, particularly those with AIDS, showed improved cognition as compared with patients receiving placebo. There were no changes in affective symptoms. The zidovudine recipients also had a statistically significant reduction in the intensity of symptomatic distress during the trial that may account in part for the observed cognitive changes. Some improvement in various cognitive measures was also seen in patients with AIDS-related complex. The results of this study suggest HIV-associated cognitive abnormalities may be partially ameliorated after the administration of zidovudine.     

Antigen-specific primary cytotoxic T lymphocyte (CTL) responses in acquired immune deficiency syndrome (AIDS) and AIDS-related complexes (ARC).

Alloantigen specific primary cytotoxic T lymphocyte (CTL) responses were examined in vitro in 10 patients with AIDS and nine with AIDS-related complex (ARC). The lymphocytes from patients with AIDS and ARC expressed significantly less (P less than 0.01) CTL activity (mean +/- s.d.; 4.7 +/- 9% and 10 +/- 11% respectively) when compared with CTL activity in normal healthy heterosexual controls (28 +/- 9.5%). When data were analysed for individual patients, lymphocytes from nine of 10 patients with AIDS and six of nine with ARC had deficient or no CTL activity. In vitro addition of purified human interleukin-2 (IL-2) during the generation of CTL resulted in significant enhancement (P less than 0.05) of CTL activity in ARC group (mean +/- s.d.; 27 +/- 18) but not in AIDS group (mean +/- s.d.; 8 +/- 8%). The presence of IL-2 augmented the induction of CTL activity in three of nine patients in AIDS group and in five of six in ARC group. In vitro addition of lectin-free supernatant (SN) obtained from cultures stimulated with PHA as well as with lymphoid cell restored the CTL functions in three of six AIDS patients and in one patient with ARC who did not respond to exogenous IL-2. The CTL activity developed in the presence of SN was higher than that manifested in the presence of IL-2 in both AIDS (SN versus IL-2; mean +/- s.d., 18 +/- 15.6% versus 8 +/- 8%) and in the ARC group (SN versus IL-2; mean +/- s.d., 35 +/- 13.9% versus 27 +/- 18.3%). Lymphocytes from three AIDS patients, however, failed to develop any CTL activity in the presence of either IL-2 or SN. These results demonstrate that: (i) the lymphocytes from majority of patients with AIDS and with ARC have deficient ability to develop into alloantigen specific primary CTL effectors, and (ii) the defective CTL functions are restored by the addition of purified IL-2 or SN in all patients with ARC and only in a subset of patients with AIDS, suggesting heterogeneity of pre-CTL to respond to IL-2 and some differentiation factor in order to differentiate in CTL effectors.     

Bone marrow examination in Egyptian patients with bicytopenia/pancytopenia

The incidences of diseases that cause peripheral blood (PB) cytopenias differ between countries according to the prevalent health problems. This study was carried out in order to identify bone marrow findings and underlying disorders in adult Egyptian patients with PB cytopenias (bicytopenia and pancytopenia). The study involved patients newly diagnosed as having PB cytopenias over a period of 1 year. Clinical and hematological parameters of patients were recorded. Bone marrow specimens were examined. Sixty-two pancytopenia and 50 bicytopenia patients were included in the study. The most common cause of pancytopenia was clonal hematopoietic disorders (34 %), hypersplenism (27 %), and aplastic anemia (21 %). The most common cause of bicytopenia was clonal hematopoietic disorders (34 %), ITP (24 %), and hypersplenism (18 %). Lymphoid neoplasms were the most common and account for 57 % of clonal pancytopenia patients and 65 % of clonal bicytopenia patients. Most hypersplenism patients (86 %) had history of hepatitis C viral infection. Our results show that, in Egypt, clonal hematopoietic disorders, hypersplenism due to chronic liver disease, ITP, and aplastic anemia are the common causes of PB cytopenias. In our setting, causes underlying bicytopenia are as important as those of pancytopenia.     

Analysis of intestinal lymphocyte subpopulations in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex

Lymphocyte subpopulations in the intestinal tissues of seven patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) were studied by immunohistologic technics at two different locations, the small bowel and the rectum. Intraepithelial and lamina propria lymphocyte subsets stained with monoclonal antibodies T11, T4, T8, and B1 were enumerated in the patients and different normal and patient control groups. Intraepithelial T11+ cells were decreased (P less than 0.05) in the small bowel of AIDS and ARC patients, primarily because of the near complete absence of T4+ lymphocytes. In the lamina propria of these patients, a depletion of T4+ cells (P less than 0.05), an increase in T8+ cells (P less than 0.05), and a reversal of the T4/T8 ratio were observed (e.g., the small bowel ratio was 0.1 +/- 0.02 vs. the normal ratio of 2.3 +/- 0.2 and the rectal ratios were 0.2 +/- 0.06 vs. normal 2.6 +/- 0.3). The T-lymphocytes in the intestine of AIDS and ARC patients did not express the receptor for interleukin-2 (IL-2). A near complete absence of T4+ lymphocytes was also seen in lymphoid follicles in the rectum. B1+ cells were not depleted. The reversal of the T4/T8 ratio, which is a hallmark of AIDS, occurs not only in the circulation but also in the gastrointestinal tissues of patients with AIDS and ARC.     

Lymph node modification in patients with the acquired immunodeficiency syndrome (AIDS) or with AIDS related complex (ARC). A histological, immuno-histopathological and ultrastructural study of 45 cases

The authors present the results of a histopathological study on the lymph-nodes taken from 45 subjects suffering from either an AIDS or from a chronic adenopathy corresponding to the definition of AIDS related complex (ARC). The various aspects observed were classed as type I to type IV. The lymph-node modifications observed in the 29 patients with an ARC could be divided into three principle groups: an extensive follicular hyperplasia associated with other elementary lesions or type IA (25 lymph-nodes from 23 patients); changes resembling a multicentric Castleman syndrome or type IB (1 case); angioimmunoblastic-like (AIL) lesions or type II (2 cases) and an association of lesions of type II (7 lymph-nodes from 6 patients). During AIDS, the adenopathy usually disappears, and the small lymph-nodes removed, especially on autopsy, show an extensive lymphoid depletion (type III) with systematic sclerosis (15 lymph-nodes from 14 patients). When adenopathy persists, it is due to infections complications (tuberculosis, cryptococcosis, avian mycobacteriosis and Whipple's disease like lesions). Of the 10 patients in whom a Kaposi's sarcoma was observed, only 6 showed lymph-node involvement, or type IV. The different histopathological lesions seem to appear according to an evolving succession, proven by certain association of lesions and by successive biopsies. In our series, 17% of subjects with an ARC evolved to AIDS. Lymph-node biopsy allows a possible ARC to be implicated on the association of the following simple lesions: follicular hyperplasia with partial or total destruction of the perifollicular lymphocytic cisterna, infiltration of the germinative centres by streams of small lymphocytes, evolving to an aspect of a "burst" germinative centre and various sinusal reactions with, in particular, the presence of neutrophilic polynuclear cells. The biopsy also allows the forms with bad prognosis to be recognized: those with AIL-like aspect or multicentric Castleman-like syndrome, which seems to represent a particular evolutive form. Finally, it also detects, in certain cases, the localization of a Kaposi syndrome, signalling the passage to AIDS. The immunopathological studies present a double interest. Firstly, they offer arguments in favour of the diagnosis: increase in the number of T8 lymphocytes in the germinative centres with the formation of small clusters and disruption of the network of dendritic reticular cells, and the inversion of the T4/T8 ratio in the extra-follicular cortical regions, by either a decrease in T4 lymphocytes or by an increase in T8 lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)     

In situ hybridization for cytomegalovirus DNA in AIDS patients.

Infection by cytomegalovirus (CMV) is a frequent cause of morbidity and mortality in patients with acquired immune deficiency syndrome (AIDS). The authors studied the distribution of CMV in 4 patients with AIDS using a commercially available, biotin-labeled CMV DNA probe for in situ hybridization and immunohistochemical staining for the detection of CMV antigen in formalin-fixed paraffin-embedded tissues. The sensitivity and specificity of the hybridization procedure was demonstrated by appropriate controls. The immunohistochemical test for the detection of CMV antigen in routine histologic sections was less sensitive than the in situ hybridization method. CMV DNA was detected not only in cytomegalic inclusion cells, but also in nuclei and cytoplasm of histologically normal-appearing cells such as endothelial cells, pneumocytes, hepatocytes, biliary epithelium, gastrointestinal epithelium, Langerhans islet cells, acinar and duct epithelium of pancreas, adrenal cortical and medullary cells, and prostate epithelium. In addition, CMV DNA, but not CMV antigen, was found in polymorphonuclear leukocytes. These cells may serve as intermediate host or reservoir of CMV and may transmit posttransfusion CMV infection. In situ hybridization on routine histologic sections with a biotinylated CMV DNA probe is a rapid, sensitive, and specific method for diagnostic and experimental pathology.     

The value of lymph node biopsy in patients with the acquired immunodeficiency syndrome (AIDS) and the AIDS-related complex (ARC): a morphological and immunohistochemical study of 90 cases

The morphological and immunohistochemical findings in lymph nodes of nine patients with the acquired immunodeficiency syndrome (AIDS) and 81 patients with the AIDS-related complex (ARC) are presented. Three basic histological patterns were observed: follicular hyperplasia (29 cases), mixed hyperplasia (49 cases) and lymphocyte depletion (12 cases). While the first two variants were detected in typical ARC patients, lymphocyte depletion was always associated with AIDS. Immunohistochemistry on frozen sections showed that the number of B-cells varied throughout the series, being higher in the follicular type and significantly lower in the lymphocyte depletion nodes. The content of T-lymphocytes of the helper/inducer (T4) phenotype was reduced in all instances; this reduction was more pronounced in the germinal centres in follicular hyperplasia, while it involved all compartments of the node in the mixed and lymphocyte depletion types. In contrast the cytotoxic/suppressor (T8) subset was increased in the follicular and mixed hyperplasias only. Partial disintegration of the dendritic network in at least some of the follicles could be demonstrated in all lymph nodes. In the follicular and mixed hyperplasias there was a high number of proliferating B-cells in the germinal centres. Our data indicate the usefulness of grading the changes occurring in lymph nodes of patients with ARC and AIDS, and allow speculation as to the pathophysiology of these conditions.     

Intra-blood-brain-barrier synthesis of HTLV-III-specific IgG in patients with neurologic symptoms associated with AIDS or AIDS-related complex

Intra-blood-brain-barrier production of virus-specific antibody is good evidence of infection within the blood-brain barrier. Patients with the acquired immuno-deficiency syndrome (AIDS) have an increased incidence of neurologic abnormalities--i.e., unexplained, diffuse encephalopathy manifested clinically as chronic progressive dementia. To define the role of human T-cell lymphotropic virus Type III (HTLV-III), the etiologic agent of AIDS, in the pathogenesis of neurologic dysfunction, we compared cerebrospinal fluid and serum from patients with neurologic symptoms associated with AIDS and the AIDS-related complex for the presence of antibodies directed against HTLV-III. Antibodies directed against HTLV-III antigens were detected by four immunologic tests: a fixed-cell immunofluorescence assay, an enzyme-linked immunosorbent assay, immunoblots of viral lysates, and immunoprecipitation of cellular lysates. All patients were seropositive, and 22 of 23 (96 per cent) had HTLV-III-specific antibodies in their cerebrospinal fluid. Unique oligoclonal IgG bands were detected in the cerebrospinal fluid, and the rate of IgG synthesis within the blood-brain barrier was elevated. In eight of nine patients tested, the enzyme-linked immunosorbent assay showed that the percentage of HTLV-III-specific IgG in cerebrospinal fluid was higher than in serum, suggesting that HTLV-III infection of neurologic tissue occurs in the majority of patients with neurologic disease associated with AIDS or its related complex.     

Evidence for activation of complement in patients with AIDS related complex (ARC) and/or lymphoadenopathy syndrome (LAS)

The complement system was examined in 16 patients with AIDS-related complex (ARC) (n = 5) and/or lymphoadenopathy syndrome (LAS) (n = 11). Of these patients 62.5% showed an impairment of classical and/or alternative pathway activity associated with the presence of cleavage fragments of C3 and/or B and a significant reduction of many complement factors. The data indicate pathological complement activation in these patients through the classical and/or alternative pathway. Complement activation was more severe in patients with ARC than in those with LAS, and greater in drug abusers than homosexuals. The lack of efficient complement in the patients can be considered an 'acquired complement deficiency' with possible importance in the failure to combat the HIV attack.     

Bone marrow examination in the koala (Phascolarctos cinereus)

A technique for bone marrow aspiration from the iliac crest in the koala (Phascolarctos cinereus) is described. Bone marrow was obtained from ten healthy koalas under general anaesthesia using the combination of tiletamine HCL and zolazepam HCL. Reference ranges were wide. The mean value for M:E was 1.7 (range 0.8–2.7), the mean percentage proliferating erythroid was 11% (range 5%–16%), and the mean percentage proliferating myeloid was 25% (range 17%–35%). In addition, bone marrow aspiration was performed on 14 koalas with various haematological diseases. Results showed aspiration to be useful in the diagnosis of leukaemia, and the investigation of regenerative anaemia and dysplastic anaemia. It was of varying use in the investigation of non-regenerative anaemia.     

Cytologic and fluorescence in situ hybridization (FISH) examination of metanephric adenoma

Metanephric adenoma is a recently described benign renal neoplasm with distinctive histologic features. The cytologic appearance and fluorescence in situ hybridization (FISH) studies of this tumor have not been described. We present a case from a 48-yr-old woman. Cytologically, the cells were arranged in tight, short papillae and loose sheets. The cells had scant cytoplasm, round monotonous nuclei with fine even chromatin and rare small nucleoli. Immunohistochemistry revealed no reactivity for epithelial membrane antigen (EMA), keratins (AE1/AE3, callus, 34BE12), or carcinoembryonic antigen (CEA). FISH showed a disomic pattern for chromosomes 7, 17, and for the chromosome 3 short arm. The differential diagnosis includes Wilms' tumor, renal adenoma, papillary renal cell carcinoma, and metastatic tumors. Both immunohistochemistry and FISH may be of help in distinguishing some of these lesions. Diagn. Cytopathol. 16:107–111, 1997. © 1997 Wiley-Liss, Inc.     

Effects of systemicin vivo interleukin-2 (IL-2) reconstitution in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) on phenotypes and functions of peripheral blood mononuclear cells (PBMC)

In the context of a clinical phase I/II therapy study with recombinant interleukin-2 (rIL-2), we monitored immunological alterations in four patients with acquired immune deficiency syndrome (AIDS) and three patients with AIDS-related complex (ARC). By determining the surface phenotypes andin vitro functions of peripheral blood mononuclear cells (PBMC) before, during, and after treatment with rIL-2, we observed transient changes in all important leukocyte subpopulations, a minor restoration of immune reactivityin vitro, and an improvement in skin reactivityin vivo. In particular, we found (i) a transient increase in C3b receptor-mediated monocyte activation in ARC patients; (ii) no influence of therapy on the otherwise intact LPS-induced interleukin-1 productionin vitro; (iii) in some patients a transient corrective influence on the high pretherapeutic immunoglobulin secretion of B cells and their nonresponsiveness to pokeweed mitogen; (iv) low T-cell responses to soluble antigens and alloantigens, which were partially restored during rIL-2 treatment in ARC patients and in one AIDS patient; (v) defective NK activity in PBMC of two AIDS patients, which was found to be restored when measured at the end of rIL-2 therapy; and (vi) a rather constant phenotypic pattern of PBMC in each patient during therapy except for the decreasing proportion of OKT9-positive lymphocytes in AIDS patients, the increasing proportion of Leu8^–Leu3a⁺ lymphocytes in all patients, and in particular, the transient significant decrease in the Leu7⁺/OKT3⁺ ratio, which pretherapeutically was very high in AIDS patients (0.78±0.21) and high in ARC patients (0.48±0.06) as compared to healthy controls (0.18±0.08).Dedicated to Prof. Dr. Dr. h. c. Otto Westphal, who continuously supported and encouraged cooperation of basic and clinical immunologists.     

Abnormal lymphocyte response to exogenous interleukin-2 in homosexuals with acquired immune deficiency syndrome (AIDS) and AIDS related complex (ARC)

Interleukin-2 (IL-2) production as well as the response of lymphocytes to exogenous IL-2 was measured in asymptomatic homosexuals, patients with acquired immune deficiency syndrome (AIDS), and homosexuals with prodromal symptoms. IL-2 production following lectin stimulation was not significantly different in homosexuals compared to age matched heterosexual controls. In contrast, the response of lymphocytes to exogenous IL-2 was significantly decreased in AIDS and homosexuals with prodromal symptoms compared to asymptomatic homosexuals and heterosexual controls. These data, combined with the data of others, suggest that an underlying immune defect in AIDS is abnormal IL-2 receptor expression and resultant poor IL-2 response.     

The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial

We conducted a double-blind, placebo-controlled trial of the efficacy of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) manifested by Pneumocystis carinii pneumonia alone, or with advanced AIDS-related complex. The subjects were stratified according to numbers of T cells with CD4 surface markers and were randomly assigned to receive either 250 mg of AZT or placebo by mouth every four hours for a total of 24 weeks. One hundred forty-five subjects received AZT, and 137 received placebo. When the study was terminated, 27 subjects had completed 24 weeks of the study, 152 had completed 16 weeks, and the remainder had completed at least 8 weeks. Nineteen placebo recipients and 1 AZT recipient died during the study (P less than 0.001). Opportunistic infections developed in 45 subjects receiving placebo, as compared with 24 receiving AZT. The base-line Karnofsky performance score and weight increased significantly among AZT recipients (P less than 0.001). A statistically significant increase in the number of CD4 cells was noted in subjects receiving AZT (P less than 0.001). After 12 weeks, the number of CD4 cells declined to pretreatment values among AZT recipients with AIDS but not amonG AZT recipients with AIDS-related complex. Skin-test anergy was partially reversed in 29 percent of subjects receiving AZT, as compared with 9 percent of those receiving placebo (P less than 0.001). These data demonstrate that AZT administration can decrease mortality and the frequency of opportunistic infections in a selected group of subjects with AIDS or AIDS-related complex, at least over the 8 to 24 weeks of observation in this study.     

Antibody specificity for human immunodeficiency virus type 1 in serum and cerebrospinal fluid from patients with AIDS and AIDS-related complex

Since little information has been reported about the specificity of antibodies to human immunodeficiency virus type 1 (HIV-1) found in the cerebrospinal fluid (CSF), 21 CSF and serum specimens were examined from 19 patients with clinical AIDS, AIDS-related complex, or asymptomatic HIV-1 infection. The predominant specificity of antibodies using Western blot analysis in both serum (100 %) and CSF (100 %) was directed towardenv gene products. The next most common antibody specificities were to thepol gene products (serum 95 %; CSF 62 %). Less commonly found was antibody to thegag-encoded proteins (serum 71 %; CSF 38 %). The level of antibody to HIV-1 in CSF could not be predicted from the level found in serum. Also, the spectrum of antibodies seen did not correlate with disease stage or with the quantity of antibody present. The serum/CSF pairs were also examined for the presence of HIV-1 antigen by commercial enzyme immunoassay. HIV-1 antigen was present in eight of 19 (43 %) of the serum samples and five of 20 (25 %) of the CSF samples tested.