Biomedical subjects

S Schubert

Publications and source records attributed to S Schubert.

At least 73 records · Page 4Linked to original sources

PubMed2000

Protein S-100beta in brain and serum after deep hypothermic circulatory arrest in rabbits: relationship to perivascular astrocytic swelling.

The aim of this study was to evaluate the relationship between the kinetic patterns of the protein S-100beta, an astroglial cell marker, and its immunohistochemical expression in the brain in rabbits that underwent cardiopulmonary bypass with deep hypothermic circulatory arrest. Fourteen New Zealand rabbits (weight, 3.1+/-0.25 kg) were anaesthetised, intubated and mechanically ventilated. Four animals were not connected to the cardiopulmonary bypass and served as controls. Ten animals were perfused according to a uniform protocol. After systemic cooling, deep hypothermic circulatory arrest was induced for 60 minutes. After reperfusion and rewarming, the animals were weaned from bypass and sacrificed. In the brain, astrocyte reactivity for S-100beta was evaluated immunocytochemically (DPC Immustain) and the serum concentrations of S-100beta were analysed using a commercially available immunoluminometric kit (Byk-Sangtec, Dietzenbach, Germany). In all experimental animals a significant increase of the serum concentration of the protein S-100beta was found immediately after reperfusion and the termination of cardiopulmonary bypass. In comparison with the control animals, increased staining of S-100beta was found in the astroglial cells and swollen astrocytic end-feet in the perivascular regions. There were fewer signs of neuronal cell injury of neurones in the hippocampus structure. In conclusion, astrocytic activation and S-100beta overexpression seems to precede the neurodegeneration following deep hypothermic circulatory arrest. The marked perivascular cell swelling may support the assumption of reperfusion injury of the astroglial cell complex that forms the blood-brain barrier, which may be indicative of the source of the released S-100beta into the blood stream.

Animals↗

PubMed2000

The effect of continuous treatment with sodium nitroprusside on the serum kinetics of the brain marker protein S-100beta in neonates undergoing corrective cardiac surgery by means of hypothermic cardiopulmonary bypass.

Neonates who undergo cardiac surgery of d-transposition of the great arteries by means of hypothermic cardiopulmonary bypass (CPB) represent a group at increased risk to develop brain injury and altered psychomotor development in early life. Measurement of protein S-100beta, an astrocytic calcium binding protein, in serum may provide information on transient astroglial cell activation and disintegration of the related blood-brain barrier due to oxidative stress during and after CPB. Conflicting results have been reported that concern the neuroprotective effect of the NO liberator sodium nitroprusside (SNP) in vitro. We evaluated the effect of continuous treatment with SNP on the serum kinetics of S-100beta in infants and children after corrective cardiac surgery. The data on 25 neonates treated intraoperatively and postoperatively and 28 without treatment were analyzed. SNP was infused (1-5 microg/kg body weight/minute depending on the haemodynamic status) after the induction of anesthesia, and during and after the termination of CPB for 2 days. Serum concentrations of S-100beta were analyzed by the use of a commercially available immunoluminometric kit (Byk-Sangtec, Dietzenbach, Germany). There were no significant differences in the bypass data between the SNP-treated and non-treated group. In comparison to the pre-bypass values, a similar increase in the concentration of protein S-100beta was found 2 hours after the termination of CPB in the SNP-treated and non-treated neonates, which decreased over the subsequent 48 postoperative hours. However, significantly lower post-bypass serum levels of S-100beta were found in the SNP-treated group after 24 hours (p = 0.0009) and 48 hours (p = 0.04) of treatment. In conclusion, the significant elevation of serum levels of protein S-100beta may indicate increased astroglial cell reactivity and increased passage into the blood stream. Longer-lasting treatment with NO liberator SNP seemed to decrease the release of S-100beta into the blood stream and may have delayed protection on the astroglial cells. The neurological significance of such an observation, however, should be evaluated in further follow-up studies, which need to include additional neurophysiological and neurodevelopmental tests.

Biomarkers↗

PubMed1999

Characterization of the integration site of Yersinia high-pathogenicity island in Escherichia coli.

The high-pathogenicity island (HPI) of virulent Yersiniae consists of (i) a functional core encoding for biosynthesis and uptake of the siderophore yersiniabactin and (ii) a 5- to 13-kb AT-rich region of unknown function. This Yersinia HPI has been shown to be widely distributed among different pathotypes of Escherichia coli. In this study, the insertion site of the HPI was defined in three different E. coli strains: The enteroaggregative E. coli (EAggEC) strain 17-2, the uropathogenic (UPEC) E. coli strain 536, and the probiotic E. coli DSM6601. We demonstrated that in all three E. coli isolates the HPI is associated with the asnT tRNA (5'-extremity) and truncated in the AT-rich region (3'-extremity) since the 17-bp direct repeat (DR) of the asn tRNA that flanks the HPI in Yersinia is missing in E. coli. Moreover, in comparison to the HPI-negative E. coli K-12 strain, a uniform deletion must have taken place in the E. coli chromosome adjacent to the 3'-border of the HPI.

Escherichia coli↗

PubMed1999

An automatic classification technique for attenuation correction in positron emission tomography.

In this paper a clustering technique is proposed for attenuation correction (AC) in positron emission tomography (PET). The method is unsupervised and adaptive with respect to counting statistics in the transmission (TR) images. The technique allows the classification of pre- or post-injection TR images into main tissue components in terms of attenuation coefficients. The classified TR images are then forward projected to generate new TR sinograms to be used for AC in the reconstruction of the corresponding emission (EM) data. The technique has been tested on phantoms and clinical data of brain, heart and whole-body PET studies. The method allows: (a) reduction of noise propagation from TR into EM images, (b) reduction of TR scanning to a few minutes (3 min) with maintenance of the quantitative accuracy (within 6%) of longer acquisition scans (15-20 min), (c) reduction of the radiation dose to the patient, (d) performance of quantitative whole-body studies.

Brain↗

PubMed1999

Comparative in-vitro activity of levofloxacin, other fluoroquinolones, doxycycline and erythromycin against Ureaplasma urealyticum and Mycoplasma hominis.

The susceptibility of 56 Ureaplasma urealyticum and 57 Mycoplasma hominis strains to levofloxacin, ofloxacin, ciprofloxacin, fleroxacin, doxycycline and erythromycin was determined by an agar dilution method. The reference strain used was M. hominis PG 21. Agar plates containing serial dilutions of antibiotics (range 0.03-16 mg/L), and control plates (without antibiotics) were inoculated with bacteria suspended in modified Shepard's broth using a multipoint inoculator. Levofloxacin showed greater activity against all U. urealyticum and M. hominis strains compared with all other antibiotics tested. The MIC90 values for U. urealyticum were as follows: levofloxacin, 1 mg/L; ofloxacin, 2 mg/L; ciprofloxacin, 4 mg/L; fleroxacin, 4 mg/L; doxycycline, 1 mg/L; erythromycin, 8 mg/L. The MIC90s for M. hominis were: levofloxacin, 1 mg/L; ofloxacin, 2 mg/L; ciprofloxacin, 4 mg/L; fleroxacin, 4 mg/L; doxycycline, 4 mg/L; erythromycin, > or = 16 mg/L. In conclusion, the results of this study suggest that levofloxacin may be useful in the treatment of mycoplasma genital infections.

Anti-Bacterial Agents↗

PubMed1999

Common and specific characteristics of the high-pathogenicity island of Yersinia enterocolitica.

Yersinia pestis, Y. pseudotuberculosis O:1, and Y. enterocolitica biogroup 1B strains carry a high-pathogenicity island (HPI), which mediates biosynthesis and uptake of the siderophore yersiniabactin and a mouse-lethal phenotype. The HPI of Y. pestis and Y. pseudotuberculosis (Yps HPI) are highly conserved in sequence and organization, while the HPI of Y. enterocolitica (Yen HPI) differs significantly. The 43,393-bp Yen HPI sequence of Y. enterocolitica WA-C, serotype O:8, was completed and compared to that of the Yps HPI of Y. pseudotuberculosis PB1, serotype O:1A. A common GC-rich region (G+C content, 57.5 mol%) of 30.5 kb is conserved between yersinia strains. This region carries genes for yersiniabactin biosynthesis, regulation, and uptake and thus can be considered the functional "core" of the HPI. In contrast, the second part of the HPI is AT rich and completely different in two evolutionary lineages of the HPI, being 12.8 kb in the Yen HPI and 5.6 kb in the Yps HPI. The variable part acquired one IS100 element in the Yps HPI and accumulated four insertion elements, IS1328, IS1329, IS1400, and IS1222, in the Yen HPI. The insertion of a 125-bp ERIC sequence modifies the structure of the promoter of the ybtA yersiniabactin regulator in the Yen HPI. In contrast to the precise excision of the Yps HPI in Y. pseudotuberculosis, the Yen HPI suffers imprecise deletions. The Yen HPI is stably integrated in one of the three asn tRNA copies in Y. enterocolitica biogroup 1B (serotypes O:8, O:13, O:20, and O:21), probably due to inactivation of the putative integrase. The 17-bp duplications of the 3' end of the asnT RNA are present in both Yersinia spp. The HPI attachment site is unoccupied in nonpathogenic Y. enterocolitica NF-O, biogroup 1A, serotype O:5. The HPI of Yersinia is a composite and widely spread genomic element with a highly conserved yersiniabactin functional "core" and a divergently evolved variable part.

Base Sequence↗

PubMed1999

A genomic island, termed high-pathogenicity island, is present in certain non-O157 Shiga toxin-producing Escherichia coli clonal lineages.

Shiga toxin-producing Escherichia coli (STEC) strains cause a wide spectrum of diseases in humans. In this study, we tested 206 STEC strains isolated from patients for potential virulence genes including stx, eae, and enterohemorrhagic E. coli hly. In addition, all strains were examined for the presence of another genetic element, the high-pathogenicity island (HPI). The HPI was first described in pathogenic Yersinia species and encodes the pesticin receptor FyuA and the siderophore yersiniabactin. The HPI was found in the genome of distinct clonal lineages of STEC, including all 31 eae-positive O26:H11/H(-) strains and 7 of 12 eae-negative O128:H2/H(-) strains. In total, the HPI was found in 56 (27.2%) of 206 STEC strains. However, it was absent from the genome of all 37 O157:H7/H(-), 14 O111:H(-), 13 O103:H2, and 13 O145:H(-) STEC isolates, all of which were positive for eae. Polypeptides encoded by the fyuA gene located on the HPI could be detected by using immunoblot analysis in most of the HPI-positive STEC strains, suggesting the presence of a functional yersiniabactin system. The HPI in STEC was located next to the tRNA gene asnT. In contrast to the HPI of other pathogenic enterobacteria, the HPI of O26 STEC strains shows a deletion at its left junction, leading to a truncated integrase gene int. We conclude from this study that the Yersinia HPI is disseminated among certain clonal subgroups of STEC strains. The hypothesis that the HPI in STEC contributes to the fitness of the strains in certain ecological niches rather than to their pathogenic potential is discussed.

Amino Acid Sequence↗

PubMed1999

Ferric enterochelin transport in Yersinia enterocolitica: molecular and evolutionary aspects.

Yersinia enterocolitica is well equipped for siderophore piracy, encompassing the utilization of siderophores such as ferrioxamine, ferrichrome, and ferrienterochelin. In this study, we report on the molecular and functional characterization of the Yersinia fep-fes gene cluster orthologous to the Escherichia coli ferrienterochelin transport genes (fepA, fepDGC, and fepB) and the esterase gene fes. In vitro transcription-translation analysis identified polypeptides of 30 and 35 kDa encoded by fepC and fes, respectively. A frameshift mutation within the fepA gene led to expression of a truncated polypeptide of 40 kDa. The fepD, fepG, and fes genes of Y. enterocolitica were shown to complement corresponding E. coli mutants. Insertional mutagenesis of fepD or fes genes abrogates enterochelin-supported growth of Y. enterocolitica on iron-chelated media. In contrast to E. coli, the fep-fes gene cluster in Y. enterocolitica consists solely of genes required for uptake and utilization of enterochelin (fep) and not of enterochelin synthesis genes such as entF. By Southern hybridization, fepDGC and fes sequences could be detected in Y. enterocolitica biotypes IB, IA, and II but not in biotype IV strains, Yersinia pestis, and Yersinia pseudotuberculosis strains. According to sequence alignment data and the coherent structure of the Yersinia fep-fes gene cluster, we suggest early genetic divergence of ferrienterochelin uptake determinants among species of the family Enterobacteriaceae.

Base Sequence↗

PubMed1998

Adaptation of active proton pumping and plasmalemma ATPase activity of corn roots to low root medium pH

Corn (Zea mays L.) root adaptation to pH 3.5 in comparison with pH 6. 0 (control) was investigated in long-term nutrient solution experiments. When pH was gradually reduced, comparable root growth was observed irrespective of whether the pH was 3.5 or 6.0. After low-pH adaptation, H+ release of corn roots in vivo at pH 5.6 was about 3 times higher than that of control. Plasmalemma of corn roots was isolated for investigation in vitro. At optimum assay pH, in comparison with control, the following increases of the various parameters were caused by low-pH treatment: (a) hydrolytic ATPase activity, (b) maximum initial velocity and Michaelis constant (c) activation energy of H+-ATPase, (d) H+-pumping activity, (e) H+ permeability of plasmalemma, and (f) pH gradient across the membranes of plasmalemma vesicles. In addition, vanadate sensitivity remained unchanged. It is concluded that plasmalemma H+-ATPase contributes significantly to the adaptation of corn roots to low pH. A restricted net H+ release at low pH in vivo may be attributed to the steeper pH gradient and enhanced H+ permeability of plasmalemma but not to deactivation of H+-ATPase. Possible mechanisms responsible for adaptation of plasmalemma H+-ATPase to low solution pH during plant cultivation are discussed.

Journal Article↗

PubMed1998

Molecular characterization of a carbon transporter in plastids from heterotrophic tissues: the glucose 6-phosphate/phosphate antiporter.

Plastids of nongreen tissues import carbon as a source of biosynthetic pathways and energy. Within plastids, carbon can be used in the biosynthesis of starch or as a substrate for the oxidative pentose phosphate pathway, for example. We have used maize endosperm to purify a plastidic glucose 6-phosphate/phosphate translocator (GPT). The corresponding cDNA was isolated from maize endosperm as well as from tissues of pea roots and potato tubers. Analysis of the primary sequences of the cDNAs revealed that the GPT proteins have a high degree of identity with each other but share only approximately 38% identical amino acids with members of both the triose phosphate/phosphate translocator (TPT) and the phosphoenolpyruvate/phosphate translocator (PPT) families. Thus, the GPTs represent a third group of plastidic phosphate antiporters. All three classes of phosphate translocator genes show differential patterns of expression. Whereas the TPT gene is predominantly present in tissues that perform photosynthetic carbon metabolism and the PPT gene appears to be ubiquitously expressed, the expression of the GPT gene is mainly restricted to heterotrophic tissues. Expression of the coding region of the GPT in transformed yeast cells and subsequent transport experiments with the purified protein demonstrated that the GPT protein mediates a 1:1 exchange of glucose 6-phosphate mainly with inorganic phosphate and triose phosphates. Glucose 6-phosphate imported via the GPT can thus be used either for starch biosynthesis, during which process inorganic phosphate is released, or as a substrate for the oxidative pentose phosphate pathway, yielding triose phosphates.

Amino Acid Sequence↗

PubMed1998

Prevalence of the "high-pathogenicity island" of Yersinia species among Escherichia coli strains that are pathogenic to humans.

The fyuA-irp gene cluster contributes to the virulence of highly pathogenic Yersinia (Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica 1B). The cluster encodes an iron uptake system mediated by the siderophore yersiniabactin and reveals features of a pathogenicity island. Two evolutionary lineages of this "high pathogenicity island" (HPI) can be distinguished on the basis of DNA sequence comparison: a Y. pestis group and a Y. enterocolitica group. In this study we demonstrate that the HPI of the Y. pestis evolutionary group is disseminated among species of the family Enterobacteriaceae which are pathogenic to humans. It prevails in enteroaggregative Escherichia coli and in E. coli blood culture isolates (93 and 80%, respectively), but is rarely found in enteropathogenic E. coli, enteroinvasive E. coli, and enterotoxigenic E. coli isolates. In contrast, the HPI was absent from enterohemorrhagic E. coli, Shigella, and Salmonella enterica strains investigated. Polypeptides encoded by the fyuA, irp1, and irp2 genes located on the HPI could be detected in E. coli strains pathogenic to humans. However, these E. coli strains showed a reduced sensitivity to the bacteriocin pesticin, whose uptake is mediated by the FyuA receptor. Escherichia strains do not possess the hms gene locus thought to be a part of the HPI of Y. pestis. Deletions of the juA-irp gene cluster affecting solely the fyuA part of the HPI were identified in 3% of the E. coli strains tested. These results suggest horizontal transfer of the HPI between Y. pestis and some pathogenic E. coli strains.

Bacterial Outer Membrane Proteins↗

PubMed1998

The yersiniabactin biosynthetic gene cluster of Yersinia enterocolitica: organization and siderophore-dependent regulation.

The ability to synthesize and uptake the Yersinia siderophore yersiniabactin is a hallmark of the highly pathogenic, mouse-lethal species Yersinia pestis, Y. pseudotuberculosis, and Y. enterocolitica 1B. We have identified four genes, irp1, irp3, irp4, and irp5, on a 13-kb chromosomal DNA fragment of Y. enterocolitica 08, WA-314. These genes constitute the yersiniabactin biosynthetic gene cluster together with the previously defined irp2. The irp1 gene consists of 9,486 bp capable of encoding a 3,161-amino-acid high-molecular-weight protein 1 (HMWP1) polypeptide with a predicted mass of 384.6 kDa. The first 3,000 bp of irp1 show similarity to the corresponding regions of the polyketide synthase genes of Bacillus subtilis and Streptomyces antibioticus. The remaining part of irp1 is most similar to irp2, encoding HMWP2, which might be the reason for immunological cross-reactivity of the two polypeptides. Irp4 was found to have 41.7% similarity to thioesterase-like protein of the anguibactin biosynthetic genes of Vibrio anguillarum. Irp5 shows 41% similarity to EntE, the 2,3-dihydroxybenzoic acid-activating enzyme utilized in enterobactin synthesis of Escherichia coli. Irp4 and Irp5 are nearly identical to YbtT and YbtE, recently identified in Y. pestis. irp3 has no similarity to any known gene. Inactivation of either irp1 or irp2 abrogates yersiniabactin synthesis. Mutations in irp1 or fyuA (encoding yersiniabactin/pesticin receptor) result in downregulation of irp2 that can be upregulated by the addition of yersiniabactin. A FyuA-green fluorescent protein translational fusion was downregulated in an irp1 mutant. Upregulation was achieved by addition of yersiniabactin but not desferal, pesticin, or pyochelin, which indicates high specificity of the FyuA receptor and autoregulation of genes involved in synthesis and uptake of yersiniabactin.

Amino Acid Sequence↗

PubMed1998

Organization and expression of rat Tspy.

We have isolated both a full-length rat Tspy cDNA from testicular mRNA by rapid amplification of cDNA ends (RACE) and RT-PCR and a full-length rat Tspy gene from genomic DNA by PCR. In contrast to the mouse, where Tspy is present in a single copy and is apparently functionless, and to man and cattle, where TSPY is organized in a moderately repetitive cluster, the rat Tspy locus apparently consists of one complete functional and one truncated, probably nonfunctional, copy, coherently localized on Yp, as revealed by FISH analysis.

Animals↗

PubMed1998

Manuscript reviewing: what reviewers have to say.

This paper reports a study that examined the experience of manuscript reviewing. Fifteen reviewers participated, responding to questions about their experience of the process, its perceived strengths and weaknesses, and areas considered worthy of further investigation. Qualitative methodology and analysis were employed. Overall, the study showed that manuscript reviewing brings both extrinsic and intrinsic rewards, but that a price must be paid for these in terms of time spent and frustrations associated with the task. There was some skepticism among reviewers about the value of the peer review process, along with a desire for improvement. Recommendations for further research centre largely around the politics of scholarship and creating a more transparent process.

Attitude of Health Personnel↗

PubMed1997

Yersinia enterocolitica promotes deactivation of macrophage mitogen-activated protein kinases extracellular signal-regulated kinase-1/2, p38, and c-Jun NH2-terminal kinase. Correlation with its inhibitory effect on tumor necrosis factor-alpha production.

The enteropathogenic bacterium Yersinia enterocolitica counteracts host defense mechanisms by interfering with eukaryotic signal transduction pathways. In this study, we investigated the mechanism by which Y. enterocolitica prevents macrophage tumor necrosis factor-alpha (TNFalpha) production. Murine J774A.1 macrophages responded to Y. enterocolitica infection by rapid activation of mitogen-activated protein kinases (MAPK) extracellular signal-regulated kinase (ERK), p38, and c-Jun NH2-terminal kinase (JNK). However, after initial activation, the virulent Y. enterocolitica strain harboring the Y. enterocolitica virulence plasmid caused a substantial decrease in ERK1/2 and p38 tyrosine phosphorylation. Simultaneously, the virulent Y. enterocolitica strain gradually suppressed phosphorylation of the transcription factors Elk-1, activating transcription factor 2 (ATF2), and c-Jun, indicating time-dependent inhibition of ERK1/2, p38, and JNK kinase activities, respectively. Analysis of different Y. enterocolitica mutants revealed that (i) MAPK inactivation parallels the inhibition of TNFalpha release, (ii) the suppressor effect on TNFalpha production, which originates from the lack of TNFalpha mRNA, is distinct from the ability of Y. enterocolitica to resist phagocytosis and to prevent the oxidative burst, (iii) the tyrosine phosphatase YopH, encoded by the Y. enterocolitica virulence plasmid, is not involved in the decrease of ERK1/2 and p38 tyrosine phosphorylation or in the cytokine suppressive effect. Altogether, these results indicate that Y. enterocolitica possesses one or more virulence proteins that suppress TNFalpha production by inhibiting ERK1/2, p38, and JNK kinase activities.

Animals↗

PubMed1997

Cavitary cryptococcoma of the lungs and meningitis by Cryptococcus neoformans in a patient with AIDS.

We report on a 39-year-old AIDS patient who presented a generalized cryptococcal disease with involvement of the lungs and central nervous system. Although the initial symptoms were mild and uncharacteristic, the radiological finding of cavernous destructions of the lungs (cryptococcoma) was detectable. The patient recovered after an initial 3 week therapy with amphotericin B and fluconazole followed by secondary prevention with fluconacole. The cavernous destructions receded within 4 months. Though the respiratory tract is the presumed port of entry for Cryptococcus neoformans, a cavernous destruction of pulmonary tissue without a diffuse infiltration of the lungs is a rare manifestation of cryptococcosis even in HIV patients.

AIDS-Related Opportunistic Infections↗

PubMed1996

Cell-cycle arrest, micronucleus formation, and cell death in growth inhibition of MCF-7 breast cancer cells by tamoxifen and cisplatin.

The induction of cell death along with cell-cycle arrest is one of the foremost mechanisms regulating cell growth. In the human breast carcinoma cell line MCF-7 we investigated two chemotherapeutic agents, the antiestrogen tamoxifen and the DNA-damaging drug cisplatin, for the relative contribution of these mechanisms to growth inhibition in culture. Growth kinetics and flow cytometry confirmed that tamoxifen at 1 microM acts mainly by arresting cells in the G0/G1 phase of the cell cycle. Compared to untreated controls, only a few more cells were detached from the monolayer and dead after a 5-day incubation. On the other hand, cisplatin at 1 microM did not induce the well-defined G2/M-arrest reported for other cell types, but resulted in a marked increase in the rate of cell death. A morphological feature observed, especially with cisplatin-treated MCF-7 cells, was the formation of numerous micronuclei (in up to 30% of the cells) and an increase in the number of binucleate cells (up to 20%). In both tamoxifen- and cisplatin- treated cultures, cell death appeared to occur by apoptosis, as indicated morphologically by cellular and nuclear shrinkage accompanied by DNA-condensation and ultimately the formation of DNA containing apoptotic bodies. However, no internucleosomal DNA degradation or endogenous endonuclease activity could be detected in the cells of the monolayer or in the mainly dead and detached cells of the culture supernatant. DNA fragmentation was only observed when isolated MCF-7 nuclei were incubated with exogenous endonucleases. However, as determined by reverse transcriptase/polymerase chain reaction amplification, MCF-7 cells do express the mRNA for DNase I, an endonuclease known to be involved in apoptosis. Thus, apoptosis is part of the growth-inhibitory process and occurs without apparent internucleosomal DNA fragmentation in MCF-7 cell cultures.

Antineoplastic Agents↗

PubMed1996

The immunomodulatory effects of antibiotics: in vitro and ex vivo investigations of 21 substances by means of the lymphocyte transformation test.

Besides their antimicrobial activity antibiotics can modulate immune response. The paper provides original data about in vitro and in vivo influence of antibiotics on lymphocyte transformation test (LTT) and gives a comprehensive overview of literature data. In the study presented here the influence of several antimicrobial substances on unstimulated and PHA-stimulated lymphocyte transformation was investigated. The proliferative response was measured as (3H) thymidine uptake by lymphocytes. For initial screening the lymphocyte transformation test was performed on murine lymphocytes in vitro. As a whole 21 antimicrobial substances were tested including representative substances of the most important main groups. As a second step experiments were done with selected substances on human lymphocytes that had shown a distinct influence on murine cells in vitro. At therapeutic concentrations a pronounced stimulation of murine lymphocyte transformation was caused by carbapenems, aminothiazole cephalosporins and imidazoles. Purine analogs had only suppressive effects. However, the increased (3H) thymidine uptake in murine cells could not be regularly reproduced in human lymphocytes and in ex vivo experiments.

Animals↗