Biomedical subjects

E Ludwig

Publications and source records attributed to E Ludwig.

At least 37 records · Page 2Linked to original sources

PubMed1998

Assessment of microsomal tolbutamide hydroxylation by a simple thin-layer chromatography radioactivity assay.

A radio thin-layer chromatographic method is described for in vitro measurement of tolbutamide methylhydroxylation as an alternative to the commonly used HPLC assay. After the incubation experiments of [14C]tolbutamide with human liver microsomes, the supernatants were directly spotted onto standard silica gel TLC plates and developed in a horizontal chamber using a solvent system consisting of toluene-acetone-formic acid (60:39:1, v/v). Dried TLC plates were exposed to a phosphor imager plate and quantificated by use of a phosphor imager. Reaction rates were calculated from the ratio of labelled metabolite to the total radioactivity. The correlation coefficient between HPLC and the TLC method was 0.978 (n=14). The described method provides a valuable tool for the determination of tolbutamide hydroxylation activity in human liver microsomes.

Chromatography, High Pressure Liquid↗

PubMed1998

Metabolism of Meloxicam in human liver involves cytochromes P4502C9 and 3A4.

1. The metabolism of Meloxicam (ME) and the cytochrome(s) P450 (CYPs) involved were analysed by using primary human hepatocytes, human liver microsomes and microsomes from recombinant human B-lymphoblastoid cell lines. 2. While human hepatocytes were capable of converting ME to a 5-hydroxymethyl metabolite (M7) and then to a 5-carboxyderivative (M5), human liver microsomes formed mostly only the 5-hydroxymethylderivative. The kinetics of the formation of M7 by human liver microsomes were biphasic with Km = 13.6 +/- 9.5 and 381 +/- 55.2 microM respectively. The corresponding Vmax were 33.7 +/- 24.2 and 143 +/- 83.9 pmol/min/mg protein respectively. 3. CYP2C9 and, to a much lesser extent, CYP3A4 were found to convert ME to M7. The involvement of 2C9 was demonstrated by inhibition of tolbutamide hydroxylase activity in the presence of ME, inhibition of ME metabolism by sulphaphenazole, correlation between ME metabolism and tolbutamide hydroxylase activity and active metabolism of ME by recombinant 2C9. The involvement of 3A4 was shown by inhibition of ME metabolism by ketoconazole, correlation between ME metabolism and nifedipine oxidase activity and metabolism of ME by recombinant 3A4. Kinetics of the formation of M7 by the individual enzymes resulted in a Km = 9.6 microM and Vmax = 8.4 pmol/min/mg protein for 2C9 and a Km = 475 microM and Vmax = 23 pmol/min/mg protein for 3A4.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1998

Cefixime in the treatment of respiratory and urinary tract infections.

Cefixime is quickly establishing in Western countries as a potent broad-spectrum antibiotic with a variety of indications. A multinational, nonrandomized study in Central and Eastern Europe has confirmed the excellent efficacy of cefixime in both children and adults. In 45 children with acute sinusitis and 50 with acute otitis media, once-daily cefixime in oral suspension resulted in clinical cure or improvement in 45 (100%) and 48 (96%) patients, respectively. In 60 adult patients with acute exacerbations of chronic bronchitis and 12 with pneumonia, cefixime 400 mg resulted in cure or improvement in 59 (98%) and 12 (100%) patients, respectively. Similarly, excellent efficacy was found in adults with urinary tract infections (UTI), with cure in 80 (94%) patients, improvement in 4 (5%), and failure in 1 (1%). Very good efficacy of cefixime was also demonstrated microbiologically, with eradication in 35 of 36 isolates from children, including all Streptococcus pneumoniae isolates, 40 of 45 isolates from patients with respiratory tract infections, and 64 of 71 isolates from patients with UTI.

Adult↗

PubMed1998

Sézary syndrome, T-helper 2 cytokines and accessory factor-1 (AF-1).

Mycosis fungoides and the Sézary Syndrome are characterized by clonal accumulation of well differentiated T-helper memory cells in the skin and, in the case of the Sézary Syndrome, also in the blood and lymph nodes. Well known immunological abnormalities in patients with MF and SS include reduced delayed type hypersensitivity, decreased proliferation upon stimulation with mitogens of the peripheral blood mononuclear cells, elevated IgE or IgA serum levels and eosinophilia. These abnormalities can be explained by the predominance of T-helper 2 cytokines. Clonal T-lymphocytes purified from the peripheral blood of SS patients transcribe mainly IL-10 and IL-5. They can be CD7 positive or negative. These clonal T cells express the accessory factor-1 (AF-1) or Interferon gamma receptor beta-chain that is essential for Interferon gamma signalling. These results imply perspectives for new therapeutical approaches, such as IL-12 or chimeric fusion proteins.

Humans↗

PubMed1997

[Study of the cost-effectiveness of sequential antibiotic (ciprofloxacin) therapy].

A multicenter, prospective, randomized study was performed to compare the cost-effectiveness of parenteral antibiotic versus parenteral antibiotic + oral ciprofloxacin sequential therapy in the treatment of moderate and severe infections in hospitalized patients. After deciding on inclusion (n = 298), the patients were randomly allocated in group "A" (evaluable 120 cases) receiving only parenteral antibiotics, or in group "B" receiving parenteral antibiotic + oral ciprofloxacin from the 3.-5. day of therapy on. The local physician decided on the starting parenteral therapy and the necessity of other therapeutic interventions, and in case of group "B" patients on the possibility of switching parenteral to oral therapy. The overall cure rate was 68% in group "A" and 82% in group "B" (improved 33 and 21, failure 5 and 1 cases resp.). Of the direct costs in patients, care, the costs of antibiotic treatments based on purchase prices was compared: the cost of antibiotic treatment in group "B" was 32% less than in group "A", and the sequential therapy saved 9000 Ft/patient in average. In conclusion, ciprofloxacin proved to be an effective antimicrobial agent that can also be used in sequential therapy and the oral administration resulted in a significant save of money with the same therapeutic effectiveness.

Adult↗

PubMed1997

[Rule-based consultation systems].

This paper overviews the architecture of rule-based consultation systems and illustrates how such systems work by an Antibiotic Advisor. Knowledge representation and the inference engine implemented in the program are briefly described along with a sample consultation with the system. The paper is concluded with an analysis of the advantages and limitations of rule-based reasoning in clinical decision support.

Anti-Bacterial Agents↗

PubMed1996

Sézary syndrome T-cell clones display T-helper 2 cytokines and express the accessory factor-1 (interferon-gamma receptor beta-chain).

Sézary syndrome (SS) is a leukemic variant of low-grade cutaneous T-cell lymphomas (CTCLs). The clonal T cells in this lymphoproliferative disorder are poorly characterized. Using antibodies against the variable region of the T-cell receptor (TCR V alpha/beta), we identified four predominant T-cell clones (two V beta 8+ clones, one V beta 5.1+, and one V alpha 2(a)+) in peripheral blood mononuclear cells (PBMC) of SS patients. Their phenotype was CD3+, CD4+, CD5+, CD45RO+. Clonal T cells were purified, and cytokine transcription and secretion was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) followed by hybridization with biotinylated probes and enzyme-linked immunosorbent assays (ELISAs). The interleukin-10 (IL-10) PCR product was cloned and sequenced and found to be identical to the published cDNA sequence. The presence of accessory factor-1 (AF-1, or interferon-gamma [IFN-gamma] receptor beta-chain) encoding mRNA was assessed by RT-PCR and immunostaining using serum of rabbits immunized with the extracellular domain of a recombinant human AF-1 protein followed by APAAP staining. Clonal T cells transcribe and secrete mainly T-helper 2 cytokines (IL-10, -5, and -13). mRNA from purified SS clones but not mRNA from SS total PBMC was positive for AF-1 in an agarose gel and/or after hybridization. AF-1 transcription was associated with membrane-bound immunoreactivity for AF-1 in SS clones. SS-derived T-cell clones display T-helper 2 cytokines. This weakens cell-mediated immunosurveillance, and explains the clinical and immunologic abnormalities in SS patients. The T-helper 2 cytokine spectrum of all clones investigated is associated with overexpression of AF-1. This suggests that AF-1 is a potential marker for these clones (and eventually other T-helper 2 lymphocytes) and might represent a target for treatment of the disease.

Base Sequence↗

PubMed1996

Analysis of free amino acids in green coffee beans. II. Changes of the amino acid content in arabica coffees in connection with post-harvest model treatment.

To investigate amino acid changes in green coffee beans in the post-harvest period, amino acid concentrations were determined in green beans and after modelled drying, fermentation and storage. After the drying at alternating temperatures up to maximally 40 degrees C, considerable changes in the concentrations of individual amino acids were identified. At the beginning of the storage period, significant changes in concentration were found to a minor extent. Under the condition of drying, it was mainly the concentration of glutamic acid that changed considerably. There was an increase in all the samples by 500 mg/kg dry matter on average, which corresponds to an increase of about 50% of the original value. In contrast, the concentration of aspartic acid in most of the samples decreased clearly due to drying. For the predominant part of the coffee samples, there was a significant increase in the hydrophobic amino acids Val, Phe, Ile and Leu. Changes of the quantities of other amino acids were non-uniform and only insignificant. Constant drying at 80 degrees C for most of the amino acids brought about only minor concentration changes compared to those values obtained at 40 degrees C. Modelled fermentation had no significant effect on the concentrations of the individual amino acids. After a 4-week storage of dried beans, amino acid concentrations did not change further. It is very possible that different post-harvest treatment parameters may influence the amount of aroma precursor compounds in the coffee beans.

Amino Acids↗

PubMed1996

Clinical outcome and immunology of postoperative arginine, omega-3 fatty acids, and nucleotide-enriched enteral feeding: a randomized prospective comparison with standard enteral and low calorie/low fat i.v. solutions.

In a prospective randomized trial in patients undergoing major abdominal surgery, the impact of a new enteral formula supplemented with arginine, omega-3 fatty acids, and nucleotides (A, n = 14) on immunological parameters was compared with a standard enteral formula (B, n = 14) and a low calorie/low fat intravenous solution (C, n = 13). Four days postoperatively, a statistically significant decrease in total leukocyte count (A, 9.0 +/- 2.9; B, 8.0 +/- 2.4; C, 11.1 +/- 3.5 x 10(6) cells/mL; A versus C, B versus C; p < 0.05), higher percentage of lymphocytes (A, 14.3 +/- 4.9; C, 8.2 +/- 6.1; p < 0.05), and decreased median CRP levels (A, 80.4 [69.9]; B, 70 [74]; C, 88.5 [142] in mg/L; A versus C, p < 0.05; B versus C; p < 0.05) were observed in the enteral nutrition groups. The expression of activated surface antigen HLA-DR was diminished on CD14+ cells over 4 d (A, 58.2 [39.2]; B, 52.2 [36.2]; C, 76.6 [25.2] in %; A versus C, p < 0.05; B versus C, p < 0.05) and 8-10 d (A, 37.9 [31.4]; C, 58.5 [37.6]; p < 0.05) postoperatively. Significantly enhanced median phagocytic activity of CD14+ monocytes and granulocytes was observed in group C 8-10 days postoperatively (A, 83.3 [11.8]; B, 71.6 [34.1]; C, 87.4 [10.8]; A versus B, B versus C, p < 0.05; and A, 75.7 [10.0]; B, 69.0 [37.8]; C, 80.0 [10.1] in %, B versus C, p < 0.05, respectively). Postoperative hospital and intensive care unit stay was similar among the three groups; however, infectious complications were less frequent in group A (A versus C, p = 0.15). Thus, a modified enteral nutritional support and supplementation may influence the immune competence toward a more efficient defense response.

Aged↗

PubMed1995

Angiotensin-converting enzyme gene polymorphism is associated with myocardial infarction but not with development of coronary stenosis.

BACKGROUND: Although both genetic and nongenetic factors contribute to the pathogenesis of coronary artery disease, the identification of specific genetic lesions has lagged behind the identification of critical environmental risk factors. A reported association between myocardial infarction (MI) and the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in European men suggests a critical role for this genomic region. However, the generality of this association remains to be determined. It also is not clear at what stage in disease progression the association with the ACE I/D polymorphism becomes important. METHODS AND RESULTS: We evaluated the ACE I/D polymorphism in patients who had undergone coronary angiography (402 men and 295 women) and in 203 representative control subjects. After polymerase chain reaction amplification, genotypes were determined by agarose gel sizing and by hybridization with allele-specific oligonucleotides. After patients were categorized by the degree of coronary artery stenosis and the occurrence of an MI, the distribution of ACE I/D genotypes was evaluated by log linear analysis. Patients were genetically representative of the regional population, and patients with > 60% stenosis of their coronary arteries had the same distribution of ACE I/D genotypes as did patients with < 10% stenosis. However, among patients with stenosis, the occurrence of an MI was significantly associated with the D allele in all patients (odds ratio [OR], 1.59; P = .002) and in men alone (OR, 1.63; P = .006). The lack of significance in women (OR, 1.40; P = .263) is probably due to the fact that only 36 women in the present study had experienced an MI. Furthermore, the association between MI and the ACE I/D polymorphism was independent of blood pressure, smoking habits, and body mass index. CONCLUSIONS: Segregation of the ACE I/D polymorphism is a pervasive genetic risk factor for MI in whites but has no evident effect on the events leading to stenosis of the coronary arteries. This suggests that risk of MI is influenced by two independent processes--atherogenesis that leads to coronary stenosis followed by conversion to MI. The renin-angiotensin system appears to confer significant risk of infarction by influencing the conversion to MI but has no apparent effect on the development of atherostenosis.

Aged↗

PubMed1995

Oxidation versus addition reactions of glutathione during the interactions with quinoid thioethers of 4-(dimethylamino)phenol.

4-(Dimethylamino)phenol (DMAP) is a potent cyanide antidote which forms many equivalents of ferrihemoglobin in vivo and in vitro. During this process formation of phenoxyl radicals was observed which are reduced by ferrohemoglobin, thereby sustaining a catalytic cycle of ferrihemoglobin formation, or which disproportionate to give the quinone imine of DMAP. In the presence of thiols, e.g., glutathione (GSH), formation of 4-(dimethylamino)-2-(glutathion-S-yl)phenol (2-GS-DMAP), 4-(dimethylamino)-2,6-bis(glutathion-S-yl)phenol (2,6-bis-GS-DMAP), and 4-(dimethylamino)-2,3,6-tris(glutathion-S-yl)phenol (2,3,6-tris-GS-DMAP) was observed. While the trisubstituted glutathione conjugate is a stable end product, 2-GS-DMAP and 2,6-bis-GS-DMAP were still reactive and produced ferrihemoglobin. It is concluded that formation of polysubstituted DMAP thioethers is a result of sequential oxidation/addition reactions with quinoid intermediates. Formation of glutathione disulfide (GSSG) was minimal during the interaction of oxidized DMAP or 2-GS-DMAP with glutathione but became significant when oxidized 2,6-bis-GS-DMAP reacted with GSH. Thus it is conceivable that the bulky glutathione substituents in 2,6-bis-GS-DMAP render the addition of a third GSH molecule to the quinone imine derivative more difficult, and other reactions may get a chance. The reaction mechanism of GSSG formation has not been fully resolved, but a radical pathway mechanism involving thiyl radicals is proposed. Oxidation and addition reactions were also observed in the absence of oxygen when ferrihemoglobin served as oxidant. In the presence of oxygen, however, GSSG formation was increased, Partly due to hydrogen peroxide formation, partly due to an additional trapping reaction of the glutathione disulfide radical anion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophenols↗

PubMed1995

Reactivity of glutathione adducts of 4-(dimethylamino)phenol. Formation of a highly reactive cyclization product.

During ferrihemoglobin formation, 4-(dimethylamino)phenol (DMAP), a potent cyanide antidote, forms a quinoid compound that is prone to sequential oxidation/addition reactions. In human red cells and hemoglobin solutions fortified with glutathione, a transient adduct has been isolated and identified as 4-(dimethylamino)-2-(glutathion-S-yl)phenol (2-GS-DMAP). This compound still formed ferrihemoglobin but differed from parent DMAP in that the reaction rate was roughly proportional to the oxygen concentration and exhibited a lag phase, pointing to a reactive autoxidation product. The compound was isolated and tentatively identified as an intramolecular cyclization product of 2-GS-DMAP. Formation of this product includes three reaction steps: (1) formation of a quinoid intermediate, (2) addition of the alpha-amino nitrogen atom of the glutamate residue to the aromatic ring, and (3) autoxidation of the cyclization product to give a highly reactive o-quinone imine. The isolated compound existed in two isomeric states (1H-NMR) which upon reduction could be separated by HPLC. The isolated reduced isomers mutually converted into each other. A model compound which was synthesized to mimic the most important structural features, 4-(dimethylamino)-6-[S-(2'-hydroxyethyl)-thio]-N-(2"-phenylethyl)-1,2- quinone imine, had a very similar visible spectum and exhibited an even higher ferrihemoglobin activity than the cyclization product. A similar phenomenon of intramolecular cyclization of a thioether of DMAP had been observed earlier: DMAP covalently bound to the SH groups of the beta-chains in hemoglobin formed a cross-link with the C-terminal histidine residue in the presence of oxygen but not in its absence.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophenols↗

PubMed1994

[Clinico-pharmacologic studies on pefloxacin].

The impact of liver impairment, renal insufficiency and age-related changes on the pharmacokinetics of pefloxacin was studied in 55 patients. The elderly patients were stratified into three age groups (61-70, 71-80 and above 81 years). The patients suffering from various infections were treated with oral or intravenous pefloxacin in a dose of 400 mg bid. Blood samples were withdrawn on the first and seventh day of therapy. The pharmacokinetics of pefloxacin was characterized by marked interindividual differences that became even more pronounced during multiple dosing. The elimination rate of pefloxacin during therapy slowed down, presumably due to its decreased metabolism. In elderly patients, the rate of cumulation is greater than in the young ones, but no significant differences could be detected among the elderly age-groups. Pefloxacin elimination also decreased in renal and hepatic impairment. There was no correlation between serum concentrations of pefloxacin and the development of adverse effects. In elderly subjects and in patients with renal or hepatic impairment, dose reduction might be considered. In mild or moderate infections or in urinary tract infections smaller doses of pefloxacin also could assure good therapeutic results. However, in severe infections especially caused by less susceptible pathogens, routine dose reduction is not recommended because of the significant interindividual differences in serum concentrations of pefloxacin.

Administration, Oral↗

PubMed1994

Analysis of free amino acids in green coffee beans. I. Determination of amino acids after precolumn derivatization using 9-fluorenylmethylchloroformate.

For the determination of free amino acids in green coffee beans, 9-fluorenylmethylchloroformate was applied successfully as the precolumn derivatization agent. The separation of the 27 free amino acids of green coffee as yet identified or quantitatively determined is almost complete. The paper describes in detail the conditions of extraction, derivatization and resolution and presents reproducible data of standard curves and of quantitative results. It has been demonstrated that by applying the extraction procedure described, 99.8% of the free amino acids detectable by this method are extracted. On principle, Arabica and Robusta coffees contain the same main and minor amino acids. It was possible for the first time to determine the free amino acids ornithine, beta-alanine and pipecolic acid quantitatively in Arabica and Robusta coffees as well as hydroxyproline in Arabica coffees.

Amino Acids↗

PubMed1994

The anti-tumour activity of ifosfamide on heterotransplanted testicular cancer cell lines remains unaltered by the uroprotector mesna.

Ifosfamide is clinically used in combination chemotherapy regimens for the treatment of patients with high-grade lymphomas, sarcomas and metastatic germ cell tumours. In order to reduce the oxazophosphorine-related urothelial toxicity, sodium mercaptoethane sulphonate (mesna) is used in different schedules following the administration of ifosfamide. The proposed mechanism of mesna activity is the binding of toxic oxazaphosphorine metabolites such as acrolein in the urine of the patients. Since an influence of mesna on ifosfamide anti-tumour activity is controversial, the current study has used xenografts from two human testicular cancer cell lines heterotransplanted into nude mice to study the anti-tumour activity of ifosfamide in combination with different dosages and schedules of mesna. In both human testicular cancer cell lines, H 12.1 and 2102 EP, ifosfamide demonstrated anti-tumour activity as a single agent. No reduction in ifosfamide activity was observed with the application of mesna at a dose range from 50% to 200% of the ifosfamide dose. Furthermore, the application of mesna before and 3 h after ifosfamide, a schedule used in many clinical protocols because of the short half life of mesna, not only maintained high ifosfamide anti-tumour activity but also seemed to be associated with the lower systemic and urothelial toxicity of ifosfamide therapy compared with ifosfamide given alone. In conclusion, the experimental in vivo system using human heterotransplanted testicular cancer cell lines confirms the significant anti-tumour activity of ifosfamide in malignant germ cell tumours and demonstrates that mesna does not impair ifosfamide anti-tumour activity in this model. These results are most likely transferable to the use of mesna in patients with metastatic testicular cancer.

Animals↗

PubMed1994

Structural requirements for the ferrihemoglobin-forming activity of glutathione S-conjugates of 4-dimethylaminophenol.

4-Dimethylaminophenol (DMAP) is a suitable cyanide antidote that rapidly forms ferrihemoglobin by catalytic transfer of electrons from ferrohemoglobin to oxygen. Deleterious methemoglobinemia, because of the catalytic cycling, is prevented by side reactions of oxidized DMAP with thiols, particularly with glutathione (GSH). In human red cells, both in vitro and in vivo, the formation of a transient bis-glutathione and a stable tris-glutathione adduct was observed. To investigate the reactivity of GSH adducts of DMAP, we synthesized various thioethers by oxidizing DMAP with PbO2 in 0.1 M sulfuric acid followed by reaction with GSH. The following compounds were isolated and characterized by 1H-NMR spectroscopy and determination of the pK values: 4-dimethylamino-2-(glutathione-S-yl)-phenol (2-GS-DMAP), 4-dimethylamino-3-(glutathione-S-yl)-phenol (3-GS-DMAP), 4-dimethylamino-2,5-bis(glutathione-S-yl)-phenol (2,5-bis GS-DMAP), 4-dimethylamino-2,6-bis(glutathione-S-yl)-phenol (2,6-bis GS-DMAP), and 4-dimethylamino-2,3,6-tris(glutathione-S-yl)-phenol (2,3,6-tris GS-DMAP). Ferrihemoglobin-forming activity was investigated with oxyhemoglobin, alkylated with N-ethylmaleimide (Hb-NES) to prevent binding of oxidized compounds to the protein SH groups. DMAP, 2,6-bis-GS-DMAP, and 2-GS-DMAP (0.1 mM each) completely oxidized Hb-NES (0.6 mM) in a decreasing order of activity (pH 7.4, 37 degrees C, air); the other derivatives were quite inactive. The same thioether reactivity was observed during autoxidation. Ferrihemoglobin formation by the reactive thioethers was greatly enhanced when the oxygen tension was increased from 2 to 100%. In contrast, variation of the oxygen tension had only marginal effects on the activity of DMAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophenols↗

PubMed1993

Response of left ventricular diastolic filling to graded exercise relative to the lactate threshold.

During incremental exercise, the left ventricular ejection fraction increases up to the intensity of the anaerobic threshold and tends to level off at higher exercise intensities. Since there is a correlation between the response of peak filling rate and ejection fraction to exercise, this study was conducted to determine whether the response of left ventricular diastolic function is similar to the response of systolic function relative to lactate threshold. Twelve healthy men performed two exercise tests on a cycle ergometer. In the first test, lactate threshold and maximal power output were determined. In the second exercise test, gated radionuclide ventriculography was performed at rest, at the lactate threshold intensity, and at peak exercise to measure ejection fraction and peak filling rate. Ejection fraction increased significantly from rest [mean (SD): 62 (5)%] to lactate threshold [76 (7)%] and did not change significantly from lactate threshold to peak exercise [77 (7)%]. Likewise, peak filling rate (normalized for stroke counts) increased from resting [6.1 (0.9) VS.s-1] to lactate threshold [9.4 (1.8) VS.s-1] and did not change significantly from lactate threshold to peak exercise [9.6 (2.9) VS.s-1]. There was no correlation between the change in peak filling rate and the change in ejection fraction from rest to lactate threshold. Thus, during incremental exercise, left ventricular diastolic function responds qualitatively similar to systolic function.

Adult↗

PubMed1993

T cell response to staphylococcal superantigens by asymptomatic HIV-infected individuals exhibits selective changes in T cell receptor V beta-chain usage.

Recognition that the murine mammary tumor C-type retrovirus and the replication-defective murine leukemia virus have "superantigen" properties raises the specter that human immunodeficiency virus might also generate T cell impairment and destruction as a result of inherent superantigen properties. The observation that individuals with AIDS lack the expression of several T cell receptor V beta-chain genes lends support to this hypothesis. Staphylococcal exotoxins represent another class of superantigen with a similar ability to stimulate large numbers of T cells bearing specific T cell receptor V beta-chain types. To examine the hypothesis that T cells from HIV-infected individuals may be exposed to a superantigen during the infection process, we have compared the ability of T cells from asymptomatic HIV-infected donors and healthy donors to respond to stimulation with several known staphylococcal exotoxin superantigens. Following in vitro stimulation with staphylococcal enterotoxin D and staphylococcal enterotoxin E, asymptomatic HIV-infected individuals responded with a significantly different T cell receptor V beta-chain usage to that observed for healthy individuals. This skewed V beta-chain usage is likely to reflect preferential conditioning of T cells bearing specific V beta-chains as a result of HIV infection, supporting the hypothesis of superantigen involvement early in the course of infection.

CD4 Antigens↗