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Biomedical subjects

V Faber

Publications and source records attributed to V Faber.

At least 37 records · Page 2Linked to original sources
PubMed1990

Fusidic acid, an immunosuppressive drug with functions similar to cyclosporin A.

Fusidic acid, a tetracyclic triterpenoic acid, is used for local and systemic treatment of bacterial infections. Its in vitro effects on the human immune response were tested. Activated blood mononuclear cells released lower levels of interleukin (IL) 1 in the presence of nontoxic and clinically attainable levels of fuscidic acid (15 to 50 micrograms/mL). In contrast, the drug failed to affect the production of two other monocyte-derived cytokines, tumor necrosis factor (TNF)-alpha and IL 6. The production of the T-cell-derived cytokines, IL 2 and interferon-gamma (IFN-gamma), were also suppressed (IC50: 5 to 15 micrograms/mL). The early costimulatory effects of IL 1 and IL 6 on mouse thymocytes and human T cells were suppressed by similar levels of the drug, as was the hybridoma growth-promoting function of IL 6. T-cell proliferation induced by phytohemagglutinin or allogeneic cells was reversibly inhibited (IC50: 15 micrograms/mL). These functions of fusidic acid were strikingly similar to those of cyclosporin A. Because of the low toxicity of the former, it may have a role as a clinically useful suppressor of immunoinflammatory processes.

Adult↗
PubMed1990

Mapping of proteoglycans in atherosclerotic lesions.

The involvement of sulphated glycosaminoglycans in atherosclerotic changes have been studied in human and rat arteries, and biochemical experiments have revealed that a significant increase in the contents of chondroitin sulphate/dermatan sulphate and cholesterol, but loss of heparan sulphate, occurs in human atherosclerotic arterial tissues. Electron micrographs have revealed that extracellular deposits of lipid are predominantly present in areas rich in chondroitin sulphate proteoglycans but not in areas rich in collagen bundles and dermatan sulphate proteoglycans. The different types of proteoglycans have been distinguished in situ by the cuprolinic blue staining method and enzymatic degradation experiments, and their topohistochemical distribution patterns analysed by morphometry of proteoglycan/cuprolinic blue precipitates. The ultracytochemical investigations indicate changes in size and pattern of chondroitin sulphate-rich proteoglycan-cuprolinic blue precipitates in human atherosclerosis. In plaque tissue, these precipitates are significantly enlarged. In addition, they accumulate around smooth muscle cells in the medial tissue. An increase in the size of proteoglycan-cuprolinic blue precipitates has also been observed in balloon catheter-induced lesions in rat carotid arteries. The large chondroitin sulphate as well as the small dermatan sulphate proteoglycan-cuprolinic blue precipitates show this alteration 2 weeks after balloon injury. We suggest that quantitative and qualitative alterations in the arterial proteoglycans occur in the pathogenesis of atherosclerosis in addition to the cell proliferation and lipid accumulation.

Animals↗
PubMed1990

Fusidic acid treatment of HIV infection: no significant effect in a pilot trial.

22 HIV-positive homosexual men were treated with fusidic acid tablets (500 mg t.i.d.) for a period of 2-12 months (mean 71/2). At entry, all had a CD4-count less than 500 X 10(6)/l, and/or a pokeweed mitogen lymphocyte proliferation response of less than 50% of 2 normal controls, and no overt opportunistic infections. No significant immunological changes were observed and no definite beneficial clinical effect. On the 10th-13th day of treatment, 12 of the patients developed fever and an itchy exanthema. The symptoms disappeared spontaneously in 9 patients. No hematological or biochemical side effects were seen. Thus, in this pilot study of fusidic acid therapy of HIV-infected men, no significant effect could be detected.

Fusidic Acid↗
PubMed1990

Aspirin reduces the growth of medial and neointimal thickenings in balloon-injured rat carotid arteries.

We analyzed the effect of Aspirin on the growth of experimentally induced vascular thickenings in rat carotid arteries. Vascular thickenings were induced by denudation of the endothelium in the left carotid artery with a balloon catheter. Administration of Aspirin-rich food (17.4 g/kg body wt/day) was started 1 week before and continued 2 weeks after injury. Nine rats were used. A control group of equal size received normal food. Sizes of the tunica media, the neointima, and the open vessel lumen were measured on cross sections of carotid segments with the aid of a videomorphometry system. The results show that in the Aspirin group, neointimal lesions are significantly smaller than in the control group (0.14 mm2 versus 0.23 mm2; p less than 0.5). Thickenings of the tunica media are also reduced (0.11 mm2 versus 0.12 mm2; p less than 0.5). It is suggested that Aspirin reduces both medial hypertrophy and neointimal outgrowth in injury-induced atherosclerosis.

Animals↗
PubMed1990

Monoclonal antibody B-ly7: a sensitive marker for detection of minimal residual disease in hairy cell leukemia.

The new monoclonal antibody (MoAb) B-ly7 was tested for its value in bone marrow diagnosis in patients with hairy cell leukemia (HCL). Cryostat sections of bone marrow biopsies were examined by an indirect immunoperoxidase technique. Lymphoma cells from all of 26 HCL cases investigated displayed strong surface membrane staining with the MoAb B-ly7, whereas tumor cells from only one of 63 patients with other lymphoproliferative disorders of B cell type reacted with this antibody. The strong reactivity of hairy cells (HCs) with this marker was not altered after therapy as demonstrated on control biopsies taken from patients treated with interferon(IFN)-alpha-2 or 2'deoxycoformycin(DCF) six-64 weeks after start of treatment. This fact as well as the very low number of B-ly7 positive cells found in a series of 13 normal bone marrow biopsies (mean: 0.3% of bone marrow cells, range: 0.0%-1.0%), which could easily be distinguished from HCs by their lower staining intensity and their morphological appearance, provided the basis for the detection of even single HCs. In our hands, in terms of sensitivity the immunohistological detection of HCs using the MoAb B-ly7 was not only superior to classical morphological techniques but also to other immunohistological parameters usually applied for this purpose. Therefore, this MoAb provides a marker for the identification of HCs, hence monitoring disease activity in HCL, and particularly for a critical response evaluation in patients undergoing treatment with IFN-alpha or DCF.

Antibodies, Monoclonal↗
PubMed1989

[Plasmapheresis in the treatment of peripheral HIV neuropathy].

Peripheral neuropathy following HIV infection is frequently seen among HIV-positive-, ARC- and AIDS patients who often complain of debilitating paresthesias. Indirect immunofluorescence technique showed antibodies directed either to myelin and/or axons and to endothelial cells of the blood vessels within the nerve tissue. Sural nerve biopsies from five patients showed demyelination, axonal degeneration and perivascular cellular infiltration. Two of the patients had nuclear inclusions and high anti-CMV titer. Plasma exchange was undertaken on five HIV infected patients which resulted in complete disappearance of symptoms in three, incomplete remission in one and no effect in one patient. The finding of autoantibodies against different nerve tissue components, cellular infiltration, positive effect of the plasma exchange and relapse suggests that autoimmunity may play a pathogenetic role in some of the HIV infected patients with peripheral neuropathy.

AIDS-Related Complex↗
PubMed1989

HIV-induced immunodeficiency. Relatively preserved phytohemagglutinin as opposed to decreased pokeweed mitogen responses may be due to possibly preserved responses via CD2/phytohemagglutinin pathway.

We studied the proliferative response of PBL to the mitogens PHA and PWM and Candida albicans Ag in 301 HIV seropositive homosexual men, of whom 55 had AIDS. The responses to PHA were reduced only in the clinically ill HIV seropositive subjects. In contrast, the responses to PWM were profoundly reduced in most HIV seropositive subjects including the asymptomatic group. Further analysis of 16 HIV seropositive subjects showed that the proliferative responses were reduced in both CD4 and CD8 T cell subsets. A total of 15 HIV seropositive individuals with low responses to PWM, of whom seven had AIDS and eight controls were chosen for the following studies. Expression of T3, Ti, delta receptors, and CD2 was investigated and showed an increased percentage of CD2 receptors positive cells in HIV seropositive subjects without AIDS. The proliferative responses of PBL to stimulation with PHA, PWM, antibodies to CD3, or antibodies to CD2 were investigated and showed significant correlation in controls, whereas in contrast, only the responses to PHA and CD2ab correlated in patients with AIDS. The proliferative responses to CD2ab and CD3ab in controls were larger than the responses to both PHA and PWM. In patients, these responses were less suppressed than the responses to PWM indicating that stimulation with mitogens is more complex than a simple stimulation of Ti/T3 and CD2 receptors. Further investigations were done on resting T cells, i.e., lymphocytes depleted of macrophages and pre-activated cells. Addition of PHA to these cells resulted in preactivation with expression of IL-2R (CD25) but not in proliferation. In contrast, addition of PHA plus SRBC, which bind to the CD2 receptors caused IL-2R expression, IL-2 production, and proliferation. Addition of PWM + SRBC did not result in proliferation. A comparison of the responses to PHA + SRBC of resting T cells from 26 HIV seropositive individuals, of whom seven had AIDS and 12 seronegative controls, showed that these responses were normal or only slightly decreased in the 19 seropositive men without AIDS whereas it was decreased in AIDS patients. Nevertheless, all AIDS patients showed clear-cut responses in this assay. Thus, the discrepancy between responses to PHA and PWM may be explained by an at least partially preserved function of the PHA/CD2-dependent pathway. We suggest that the defect induced by the HIV infection primarily concerns T3/Ti-induced responses.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Prognostic value of immunologic abnormalities and HIV antigenemia in asymptomatic HIV-infected individuals: proposal of immunologic staging.

The prognostic value of various immunologic tests was investigated in 150 HIV-seropositive homosexual men, who were initially without HIV-related symptoms or AIDS and who were followed for a median of 12 months (range 3-28 months). The laboratory investigations included HIV antigen in serum, total lymphocyte count, T-helper (CD4) and T-cytotoxic/suppressor (CD8) counts, and lymphocyte transformation responses to the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM), and to antigenic extracts from Candida albicans and cytomegalovirus. 24 individuals developed HIV-related symptoms or AIDS (11 cases). All parameters except the CD8 count were of prognostic value, but a multivariate analysis of symptom-free survival showed that HIV antigenemia, a CD4 count less than 0.5 x 10(9)/l, and relative response to PWM below 25% of controls contained all the prognostic information. Individuals abnormal at entry for these 3 variables had a theoretical 36 times as high hazard of developing symptoms within the observation period as had individuals with normal parameters. There was no significant covariation between HIV antigenemia on the one hand and CD4 count and response to PWM on the other. Although, the latter 2 variables covaried, each of them provided independent information, and both were used to classify the degree of the immunodeficiency in 3 stages: Im-0 with normal values, Im-1 with one, and Im-2 with both tests abnormal. Individuals in stage Im-2 had a 10 times increased risk of developing symptoms. The immunologic staging correlated significantly with the clinical grouping (CDC criteria). This staging improved in only 1, but deteriorated in half of 36 individuals observed for at least 18 months. Thus, the staging is likely to prove useful when attempts to arrest the immunodeficiency of HIV-infected individuals has to be monitored.

Biomarkers↗
PubMed1989

Human papilloma virus type 11 in a fatal case of esophageal and bronchial papillomatosis.

We report a case of an apparently healthy 27-year-old man with a fatal course of papillomatosis, originating in the distal part of the esophagus and spreading into the main and intermediate bronchus. Human papillomavirus type 11, usually associated with juvenile laryngeal papillomatosis and genital condyloma acuminatum, was detected in the papillomas. In spite of treatment with CO2-laser evaporation of the papillomas, and with systemic as well as topical interferon, VP-16 and bleomycin, the papillomatosis progressed relentlessly during almost 2 years, and finally caused the death of the patient. We have no explanation for the malignant course of wart virus infection in this young man.

Adult↗
PubMed1989

Type I reactions directed against Pneumocystis carinii in AIDS patients.

Type I allergy directed against Pneumocystis carinii (PC) has been investigated in 14 patients with AIDS. The Pneumocystis carinii pneumonia often shows a rapid and severe course, and type I allergy against the parasite might be a pathogenic co-factor in the interstitial lung inflammation. In twelve of the AIDS patients the clinical symptoms and course of illness indicated a PC pneumonia. The basophil histamine release test was used as a sensitive test to detect type I allergy against PC. Eight of the patients showed significant histamine release when stimulated with PC. In contrast, only two patients in the group of 12 HIV antibody-positive homosexual men and none in the control group of 13 heterosexual men released histamine. The histamine release was mediated by an immunological reaction, since the release was abolished and regained by removal from and refixation to the cell surface of the cell-bound immunoglobulins before the antigen challenge. The results suggest an involvement of type I allergy as a pathogenic co-factor in Pneumocystis carinii pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Decreased B lymphocyte ecto-5'nucleotidase and increased adenosine deaminase in mononuclear cells from patients infected with human immunodeficiency virus.

The levels of purine enzyme activities were studied in 10 patients with acquired immunodeficiency syndrome (AIDS) or AIDS related complex (ARC) and in 6 healthy individuals with antibodies against human immunodeficiency virus (HIV). All AIDS/ARC patients studied had ecto-5'nucleotidase (ecto-5'NUC) activity in B lymphocytes below the normal range and 4 out of 6 clinically healthy HIV-positive likewise had reduced activity. Increased numbers of activated B lymphocytes were found both in the group of healthy HIV positive individuals and in AIDS/ARC patients. Further studies are needed to define whether the decrease in ecto-5'NUC activity on the B lymphocytes is a result of increased activation of the cells or of a B cell defect. No significant changes were found in ecto-5'NUC levels in T lymphocytes or mononuclear cells (MNC), neither in the group of AIDS/ARC patients nor in the healthy HIV-positive group. Both AIDS/ARC patients and healthy individuals with antibodies against HIV had increased levels of adenosine deaminase (ADA) activity in mononuclear cells, but only in the group of AIDS/ARC patients was the increase significant. No changes were found in purine nucleoside phosphorylase (PNP) activity in the two groups tested. From these investigations of purine enzyme levels and other markers of immune function in both sick and healthy HIV infected individuals we conclude that the observed changes in ecto-5'NUC and ADA activities in HIV infected patients are not a direct result of the HIV infection but develop early in the course of the disease.

5'-Nucleotidase↗
PubMed1988

Anti-corticosteroid antibodies in AIDS patients.

Patients suffering from AIDS tend to have symptoms that resemble those encountered in adrenocortical insufficiency. Serum sodium concentrations and blood pressure values were monitored and found to be subnormal, despite the fact that renin activity and aldosterone levels were either normal or elevated. We report the presence of autoantibodies directed against hydrocortisone among such AIDS patients. Indirect immunofluorescence technique using patients' sera and adrenal glands from AIDS patients as antigen showed antibodies to adrenocortical cells in sera from 9 of the 12 AIDS patients and in none from patients with autoimmune diseases and viral diseases or healthy blood donors. No similar reaction was seen in normal human or monkey adrenal glands. An ELISA technique was developed using hydrocortisone as antigen and using this technique 45% of the AIDS patients were found to have antibodies to hydrocortisone. It is possible that anti-corticosteroid antibodies (ACSA) may play a role in the pathophysiology of the Addison's like syndrome seen in terminal phases of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Yield of diagnostic tests for opportunistic infections in AIDS: a survey of 33 patients.

To examine the therapeutic consequences of diagnostic tests for AIDS-related infections, case records from 33 deceased AIDS patients were reviewed; 23 were autopsied. Determination of serum antibody titres was not important. In particular, there was no relation between titres and isolation of cytomegalovirus (CMV); isolation attempts or possibly antigen determination would be better. Samples for CMV isolation were obtained from 31 patients; only 7 were negative. Blood, faeces, and particularly sputum cultures gave a low yield; the number of such examinations could be reduced considerably. However, 4/7 disseminated infections with atypical mycobacteria were only revealed at autopsy, despite numerous cultures in vivo. Liver biopsies were not helpful. Diagnostic procedures for Pneumocystis carinii pneumonia by lung biopsy caused pneumothorax in 3/15 patients; bronchoalveolar lavage or treatment/prophylaxis without diagnosis could be considered. In 8 autopsies, microscopy was suggestive of cerebral toxoplasmosis, but only 1 patient had presented important clinical symptoms. We suggest a schedule with regular microbiologic and parasitic examinations and few antibody tests, but with more antigen tests.

Acquired Immunodeficiency Syndrome↗