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A Rubbert

Publications and source records attributed to A Rubbert.

At least 37 records · Page 2Linked to original sources
PubMed1998

Dendritic cells express multiple chemokine receptors used as coreceptors for HIV entry.

Cells of the dendritic lineage are thought to be among the first cells infected after mucosal exposure to HIV. In this study, we have identified the presence of multiple chemokine receptors on dendritic cells (DC) that may function as coreceptors for HIV entry. DC effectively used CCR5 for entry of macrophage (M)-tropic isolates. CCR3, the eotaxin receptor, initially identified on eosinophils, is expressed on DC and may be used as an entry coreceptor by certain dual-tropic strains. CXCR4 was not expressed on DC, although SDF-1 induced a calcium flux and DC could be infected by T cell line (T)-tropic HIV. Our findings provide evidence for the presence of a non-CXCR4 SDF-1 receptor on DC that is used mainly by T-tropic strains of HIV. DC from individuals homozygous for a 32-bp deletion of the CCR5 gene are also infectable with M-tropic strains of HIV-1, and this infection is inhibited by stromal cell-derived factor (SDF)1, suggesting that this receptor can also be used by M-tropic HIV for entry. Delineation of the spectrum of coreceptor usage on DC may offer new approaches to interfere with the initiation and propagation of HIV infection.

Base Sequence↗
PubMed1997

Macrophage-tropic HIV and SIV envelope proteins induce a signal through the CCR5 chemokine receptor.

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) enter target cells by forming a complex between the viral envelope protein and two cell-surface membrane receptors: CD4 and a 7-span transmembrane chemokine receptor. Isolates of HIV that differ in cellular tropism use different subsets of chemokine receptors as entry cofactors: macrophage-tropic HIVs primarily use CCR5, whereas T-cell-tropic and dual-tropic isolates use CXCR4 receptors. HIV-mediated signal transduction through CCR5 is not required for efficient fusion and entry of HIV in vitro. Here we show that recombinant envelope proteins from macrophage-tropic HIV and SIV induce a signal through CCR5 on CD4+ T cells and that envelope-mediated signal transduction through CCR5 induces chemotaxis of T cells. This chemotactic response may contribute to the pathogenesis of HIV in vivo by chemo-attracting activated CD4+ cells to sites of viral replication. HIV-mediated signalling through CCR5 may also enhance viral replication in vivo by increasing the activation state of target cells. Alternatively, envelope-mediated CCR5 signal transduction may influence viral-associated cytopathicity or apoptosis.

CD4 Antigens↗
PubMed1997

Multifactorial nature of noncytolytic CD8+ T cell-mediated suppression of HIV replication: beta-chemokine-dependent and -independent effects.

Chemokines were originally characterized by their ability to direct migration and induce activation of selected leukocyte populations. The beta-chemokines MIP-1 alpha, MIP-beta, and RANTES have been implicated in the suppression of viral replication by CD8+ T cells from HIV-infected individuals. The present study was undertaken to evaluate the effect of beta-chemokines on HIV replication in cocultures of dendritic cells (DCs) and CD4+ T cells, and an in vitro model of the lymphoid microenvironment. In the acute infection system, where DCs from uninfected individuals are pulsed with HIV and cocultured with autologous CD4+ T cells, no inhibition of replication of monocytotropic or T cell tropic viral isolates by MIP-1 alpha, MIP-1 beta, and RANTES, alone or in combination, was observed. In contrast, in an endogenous infection system, where the DCs and CD4+ T cells were obtained from HIV-infected subjects, addition of recombinant beta-chemokines suppressed HIV replication. However, neutralizing antibodies to beta-chemokines did not affect the suppressive activity of CD8+ T cells from HIV-infected donors in either system, suggesting that CD8+ T cell-mediated suppression is not due exclusively to beta-chemokines. Furthermore, no significant differences in secretion of MIP-1 alpha, MIP-1 beta, and RANTES by purified CD8+ T cells were noted in uninfected versus HIV-infected donors, regardless of the stage of disease. These results indicate that HIV suppression by CD8+ T cells derived from HIV-infected donors is a multifactorial phenomenon and not limited to the action of MIP-1 alpha, MIP-1 beta, and RANTES.

CD4-Positive T-Lymphocytes↗
PubMed1997

Longitudinal development of distress, coping and quality of life in HIV-positive persons.

BACKGROUND: Longitudinal study on burdens, quality of life and coping strategies of HIV-positive persons to identify patterns of successful adaptation to the demands of the infection. METHODS: In a semiprospective multimodal approach, 61 HIV-positive persons in all stages of the infection attending an HIV ambulatorium were assessed by inventories (3 times) and by a half-standardized interview (baseline T1 focussing on first reactions after diagnosis, follow-up T3 1.5 years later). Subjects had a mean age of 35.3 years and 69% were male. Forty-four percent were infected via homosexual intercourse, 46% via intravenous needle sharing and 10% via heterosexual intercourse or an unknown source. RESULTS: Global, psychic and familial distress decreased significantly from the first period after the diagnosis of HIV to the third time of measurement, while somatic complaints increased. Most test persons were able to deal effectively with the demands of the infection and showed a great degree of flexibility in their use of cognitive-actional and emotional-palliative strategies; they achieved a high quality of life. In contrast, highly distressed individuals, mainly drug users, tended to cope in an evasive-regressive way and reported a low quality of life. Correlations between ineffective coping strategies and low quality of life were found to be significant. CONCLUSIONS: After an initial phase of sorrow and lack of orientation regarding their future life, most HIV-positive persons deal effectively with the demands of the HIV infection and report a good quality of life. In contrast, HIV-positive persons with a high degree of distress and an evasive-regressive coping pattern need professional support, such as psychotherapy.

Adaptation, Psychological↗
PubMed1997

Inherited resistance to HIV-1 conferred by an inactivating mutation in CC chemokine receptor 5: studies in populations with contrasting clinical phenotypes, defined racial background, and quantified risk.

BACKGROUND: CC chemokine receptor 5 (CCR5) is a cell entry cofactor for macrophage-tropic isolates of human immunodeficiency virus-1 (HIV-1). Recently, an inactive CCR5 allele (designated here as CCR5-2) was identified that confers resistance to HIV-1 infection in homozygotes and slows the rate of progression to AIDS in heterozygotes. The reports conflict on the effect of heterozygous CCR5-2 on HIV-1 susceptibility, and race and risk levels have not yet been fully analyzed. Here we report our independent identification of CCR5-2 and test its effects on HIV-1 pathogenesis in individuals with contrasting clinical outcomes, defined race, and quantified risk. MATERIALS AND METHODS: Mutant CCR5 alleles were sought by directed heteroduplex analysis of genomic DNA from random blood donors. Genotypic frequencies were then determined in (1) random blood donors from North America, Asia, and Africa; (2) HIV-1+ individuals; and (3) highly exposed-seronegative homosexuals with quantified risk. RESULTS: CCR5-2 was the only mutant allele found. It was common in Caucasians, less common in other North American racial groups, and not detected in West Africans or Tamil Indians. Homozygous CCR5-2 frequencies differed reciprocally in highly exposed-seronegative (4.5%, n = 111) and HIV-1-seropositive (0%, n = 614) Caucasians relative to Caucasian random blood donors (0.8%, n = 387). This difference was highly significant (p < 0.0001). By contrast, heterozygous CCR5-2 frequencies did not differ significantly in the same three groups (21.6, 22.6, and 21.7%, respectively). A 55% increase in the frequency of heterozygous CCR5-2 was observed in both of two cohorts of Caucasian homosexual male, long-term nonprogressors compared with other HIV-1+ Caucasian homosexuals (p = 0.006) and compared with Caucasian random blood donors. Moreover, Kaplan-Meier estimates indicated that CCR5-2 heterozygous seroconvertors had a 52.6% lower risk of developing AIDS than homozygous wild-type seroconvertors. CONCLUSIONS: The data suggest that homozygous CCR5-2 is an HIV-1 resistance factor in Caucasians with complete penetrance, and that heterozygous CCR5-2 slows the rate of disease progression in infected Caucasian homosexuals. Since the majority (approximately 96%) of highly exposed-seronegative individuals tested are not homozygous for CCR5-2, other resistance factors must exist. Since CCR5-2 homozygotes have no obvious clinical problems, CCR5 may be a good target for the development of novel antiretroviral therapy.

Adult↗
PubMed1996

99m-Tc-HMPAO-SPECT in diagnosis of early cerebral vasculitis.

The objective of this study was to evaluate whether mild neurological symptoms suggestive of neuropsychiatric involvement may be associated with cerebral perfusion defects as detected by functional brain imaging with 99m-Tc-HMPAO-SPECT (single photon emission computed tomography). SPECT analysis for the early detection of central nervous system (CNS) involvement was evaluated in 40 consecutive patients with systemic vasculitis or with Sneddon's syndrome. Of these, 18 patients showed overt neuropsychiatric symptoms, so-called major symptoms (e.g. motoric or sensible defects); 6 had mild symptoms like headache or cognitive disorders, so-called minor symptoms: 16 patients did not present with any of these symptoms. SPECT abnormalities were detected in 16 of the 18 patients with overt neuropsychiatric symptoms (89%). Five of the 6 patients with minor symptoms (83%) and 5 of the 16 patients without neurological symptoms (31%) also had SPECT abnormalities. There was no relation to disease activity or duration. We concluded that the high sensitivity of SPECT (87.5%) in detecting perfusion abnormalities among the evaluated group of patients indicates its suitability for early diagnosis of vasculitic CNS involvement.

Adult↗
PubMed1995

99mTc-trimethyl-BrIDA scintigraphy in HIV-related cholangiopathy.

A HIV-infected 37-year-old man with diffuse mid-abdominal pain and elevated liver enzymes was sequentially studied by sonography, computed tomography (CT), 99mTc-trimethyl-BrIDA scintigraphy and endoscopic retrograde cholangiopancreatography (ERCP). CT and sonography did not lead to a final diagnosis. Cholescintigraphy showed signs of cholecystitis and sclerosing cholangitis with intra- and extrahepatic bile duct dilatation. These findings could be confirmed by ERCP, rendering HIV-associated cholepathy probable. Cytomegalovirus infection was demonstrated by polymerase chain reaction from bile fluid and the presence of cryptosporidia infection in a histology specimen isolated by ERCP. Therefore, biliary scintigraphy seems promising for screening for HIV-associated cholangio- and cholecystopathy, being less invasive and less bothering for the patient than ERCP.

Adult↗
PubMed1994

Evidence for direct anti-heparin-sulphate reactivity in sera of SLE patients.

Recently it has been suggested that anti-ds-DNA antibodies (Abs) promote tissue damage in systemic lupus erythematosus (SLE) by cross-reactivity with highly negatively charged tissue components such as heparan sulphate (HS), the major glycosaminoglycan of the glomerular basement membrane (GBM). Other authors, however, support the theory of DNA-anti-dsDNA immune complex deposition in situ. To further elucidate the possible role of HS antibodies, we developed a new ELISA system with heparan sulphate bound to solid phase. SLE patients (n = 40) showed a higher reactivity against HS (mean = 28.4, SD = 34.3) as compared to normal donors (n = 28, mean = 15.2, SD = 6.3) and patients with rheumatoid arthritis (n = 35, mean = 14.3, SD = 6.4). The addition of native dsDNA or HS to SLE sera was followed by a dose-dependent reduction in anti-HS reactivity. In contrast, in an anti-dsDNA ELISA, no reduction was observed when HS was added to SLE sera. An increase in reactivity was observed when SLE sera with and without a prior incubation with dsDNA were digested with DNAse I or II. After the purification of serum samples by protein A sepharose under dissociative conditions, seven out of eight SLE patients showed an increase in anti-HS reactivity. No correlation of the anti-HS Abs was found with organ involvement or other serological parameters. We concluded, that there is evidence for a direct anti-HS Ab reactivity in SLE sera. A part of these antibodies seems to show low avidity anti-dsDNA cross-reactivity.

Antibodies, Anti-Idiotypic↗
PubMed1994

Anticardiolipin antibodies in HIV infection: association with cerebral perfusion defects as detected by 99mTc-HMPAO SPECT.

Anticardiolipin antibodies (ACA) belong to a heterogeneous group of antibodies directed against negatively charged phospholipids. In patients with rheumatic disorders, their presence has been correlated to the occurrence of thromboembolic complications, thrombocytopenia, abortions and other disease manifestations. Several studies have revealed the detection of mostly high-titre ACA in a significant proportion of HIV-infected patients without any known clinical relationship. In our study, ACA were detected in 17/34 HIV-infected patients, and their presence was significantly associated with the detection of cerebral perfusion abnormalities by 99mTc-HMPAO SPECT. SPECT scans were classified as normal or as focal or diffuse defects in uptake. Most patients (13/16) with cerebral perfusion defects had elevated ACA titres in contrast to 4/18 patients with normal SPECT findings (P = 0.002). Focal uptake defects were always associated with the presence of ACA. No correlation to clinical features or other laboratory parameters was evident. Our results suggest a possible implication of autoimmune mechanisms in the pathogenesis of cerebral perfusion abnormalities detected by SPECT scanning in HIV-infected patients. However, further studies are needed to evaluate the clinical significance and to develop possible therapeutic consequences.

AIDS-Related Opportunistic Infections↗
PubMed1993

Single-photon-emission computed tomography analysis of cerebral blood flow in the evaluation of central nervous system involvement in patients with systemic lupus erythematosus.

OBJECTIVE: Single-photon-emission computed tomography (SPECT) scanning was used to detect potential central nervous system (CNS) involvement in patients with systemic lupus erythematosus (SLE), by determining cerebral blood flow abnormalities. METHODS: SPECT scans were performed on 35 SLE patients, grouped into 3 categories: those without neuropsychiatric symptoms (n = 10), those with definite neurologic or psychiatric disorders (n = 10), and those with mild symptoms such as headache or memory disturbances (n = 15). SPECT scan features were classified as normal or as focal or diffuse defects in uptake. RESULTS: SPECT findings were normal in 9 of the 10 patients without CNS symptoms, and abnormal in 9 of the 10 patients with overt neuropsychiatric disease (with motor or sensory deficits). Interestingly, only 4 of the 15 patients (26.7%) with mild symptoms suggestive of CNS disease had normal SPECT findings; the 11 remaining patients showed focal (53.3%) or diffuse (20%) uptake defects. An association between SPECT findings and disease duration was also observed, but there was no correlation of SPECT results with overall disease activity, serologic findings, or medications used. CONCLUSION: Our data suggest that in a substantial proportion of patients, SPECT analysis may provide additional information on potential CNS involvement, and may therefore be useful in therapeutic decision-making and disease monitoring in order to prevent CNS damage.

Adult↗
PubMed1993

[Intravenous administration of immunoglobulins in systemic lupus erythematosus: review of the literature and initial clinical experiences].

About 10 years ago, the first reports about the successful treatment of autoimmune thrombocytopenia with high-dose intravenously administered immunoglobulins (ivIg) were published. Since this time ivIg have been tried for treating almost any autoimmune disease. However, reports about this treatment modality are only anecdotal. So far, ivIg are a widely used and accepted treatment only for autoimmune thrombocytopenia and Kawasaki disease. During the last years many groups tried to gain a better understanding of the mechanisms by which ivIg exert their effects in autoimmune diseases. In systemic lupus erythematosus (SLE) only case reports are available which describe encouraging positive effects of ivIg especially in patients with cytopenia and vasculitis. However in some cases a serious impairment of renal function after ivIg therapy has been reported. This was seen mainly in SLE patients who already had renal involvement before ivIg therapy was started. Therefore, extreme caution should be exercised in these patients until we know more about the pathophysiology of this side effect. We have treated 6 SLE patients with high-dose ivIg (400 mg/kg, 5 days). One patient had a remission for 6 months, another patient for 36 months; in 2 patients with preexisting reduced renal function we observed two acute renal failures and in 1 patient a decrease of the renal function 1 month after ivIg treatment. These preliminary data demonstrate the necessity of controlled clinical trials to prove the effectiveness, to define indications, to find the optimal dosage, and to study the possible mechanisms of action.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Multiple chromosomal changes and karyotypic evolution in a patient with myelofibrosis.

Several subclones were identified in unstimulated peripheral blood cells from a patient with chronic myeloproliferative disease, which was classified as myelofibrosis by morphologic terms. These subclones were characterized by an unusual number of different karyotype anomalies. Some of the more complex chromosomal rearrangements could be clearly defined by fluorescence in situ hybridization. Chromosome arms involved in clonal aberrations were 1q, 3p, 6p, 7q, 11q, 13q, 15q, 17q, 18p, and 20q. Reconstruction of karyotype evolution was attempted by karyotypic analysis of 100 metaphase spreads each in two separate investigations.

Aged↗
PubMed1991

Functional characterization of tumor-infiltrating lymphocytes, lymph-node lymphocytes and peripheral-blood lymphocytes from patients with breast cancer.

Mononuclear cell infiltration is frequently seen within human solid tumors. Effector cells within the tumor site usually fail to exhibit cytotoxic or natural killer activity when freshly isolated; however, they develop potent and sometimes specific cytotoxicity after expansion in IL2. Thus, local tumor environment may influence lymphocyte function. In our study, we disaggregated human breast-cancer and lymph-node tissue to obtain lymphocyte-enriched cell fractions. Besides phenotypic analysis, functional characterization with regard to proliferation and cytokine production of tumor-infiltrating lymphocytes (TIL), peripheral-blood lymphocytes (PBL) and lymph-node lymphocytes (LNL) was the aim of our study. TIL showed an enrichment of CD8+ cells with a corresponding decrease in CD4+ cells in comparison with PBL and LNL. In response to PHA, TIL showed decreased 3H-thymidine uptake, but TIL were significantly stimulated by rhIL2. TIL produced low levels of IL2, TNF and IFN gamma upon mitogen/phorbol ester stimulation, while PBL produce high levels of TNF and IFN gamma but low levels of IL2. Under the same experimental conditions, LNL produce high levels of TNF and IL2 but low levels of IFN gamma. Mitogen-mediated TNF secretion was increased after addition of autologous tumor cells in TIL and LNL, whereas IFN gamma secretion tended to be suppressed. Our results indicate different patterns of activities of TIL, LNL and PBL from breast-cancer patients.

Breast Neoplasms↗
PubMedDate not supplied

Pregnancy course and complications in patients with systemic lupus erythematosus.

Among 165 patients with systemic lupus erythematosus (SLE), we observed 21 pregnancies in 19 patients since 1987. The mean duration of disease at the time of pregnancy was 4.5 +/- 3 years. All but three patients required immunosuppressive treatment before and during pregnancy. The effect of pregnancy on the course of SLE was studied. Severe disease exacerbations were rare and largely confined to patients with renal involvement. Most patients showed elevated titers of dsDNA antibodies during pregnancy but clinical activity of disease was usually mild. Complement C3 decrease appeared to be the most sensitive marker for pregnancy-related complications. The detection of antibodies to phospholipids was frequent during pregnancy in contrast to a low prevalence before and after pregnancy. Their presence could be associated with intrauterine growth retardation. Preterm delivery before the 37th week of pregnancy had to be performed in the majority of patients. None of the patients experienced abortion although three patients had to delivered in the 29th week of pregnancy because of increasing symptoms of pre-eclampsia. Two of these children died and the third child suffered from intracranial hemorrhage in the early postpartum period. Our data demonstrate that successful pregnancy outcome was related to a gestational age of more than 32 weeks, making careful monitoring and appropriate therapeutic management necessary.

Adult↗