Biomedical subjects

S Michel

Publications and source records attributed to S Michel.

At least 19 recordsLinked to original sources

PubMed2006

Fluorescent microspheres reveal different regional blood flow in hyperacutely rejected nontransgenic and hDAF pig hearts.

Classic features of hyperacute rejection show differential severity in the inner compared to the outer myocardium. In the present study, regional blood flow (RBF) measured by fluorescent microspheres served as a marker of the extent of hyperacute rejection. Using a working heart model, hearts of nontransgenic and hDAF transgenic pigs were perfused with human blood. Additionally, hDAF transgenic pig hearts were perfused with human blood containing GAS914 or the GPIIb/IIIa inhibitor tirofiban. Injections of fluorescent microspheres into the donor heart were performed in situ and during perfusion. Reference arterial blood samples were collected from the inferior aorta and the afterload line. Perfusion was terminated before hyperacutely rejected hearts failed to pump against the afterload column. RBF was determined in tissue samples of standardized areas of the left atrium and ventricle. Each specimen was divided into subepicardial and subendocardial tissue samples. Fluorescence intensity was measured using an automated luminescence spectrometer. At the end of perfusion with human blood, hyperacutely rejected nontransgenic pig hearts showed a higher RBF in the subendocardium. In hDAF-transgenic pig hearts perfused with unmodified human blood the subendocardial/subepicardial blood flow ratio changed in favor of the subepicardium. This ratio was not further improved by GAS914. In contrast, tirofiban was able to assimilate subepicardial and subendocardial blood flow. In conclusion, RBF of hyperacutely rejected pig hearts was inhomogeneous. Inhibition of complement activation improved the reduced subepicardial RBF, but depletion of antibodies had no positive effect. The ability of tirofiban to further increase subepicardial RBF affirms thrombosis of subepicardial veins as the defining characteristic of hyperacute rejection.

Acute Disease↗

PubMed2006

Brain-derived neurotrophic factor and neurotrophin receptors modulate glutamate-induced phase shifts of the suprachiasmatic nucleus.

Light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells. Previous work raised the possibility that brain-derived neurotrophic factor (BDNF) and its high-affinity tropomyosin-related receptor kinase may be important as modulators of this excitatory input into the SCN. In order to test this possibility, we used whole-cell patch-clamp methods to measure spontaneous excitatory currents in mouse SCN neurons. We found that the amplitude and frequency of these currents were increased by BDNF and decreased by the neurotrophin receptor inhibitor K252a. The neurotrophin also increased the magnitude of currents evoked by application of N-methyl-d-aspartate and amino-methyl proprionic acid. Next, we measured the rhythms in action potential discharge from the SCN brain slice preparation. We found that application of K252a dramatically reduced the magnitude of phase shifts of the electrical activity rhythm generated by the application of glutamate. By itself, BDNF caused phase shifts that resembled those produced by glutamate and were blocked by K252a. The results demonstrate that BDNF and neurotrophin receptors can enhance glutamatergic synaptic transmission within a subset of SCN neurons and potentiate glutamate-induced phase shifts of the circadian rhythm of neural activity in the SCN.

Animals↗

PubMed2006

Multicolor FISH used for the characterization of small supernumerary marker chromosomes (sSMC) in commercially available immortalized cell lines.

There are only about 30 commercially available cell lines which include small supernumerary marker chromosomes (sSMC). As approximately 2.5 million people worldwide are carriers of an sSMC, this small number of immortalized cell lines is hard to understand. sSMC cell lines provide practically unlimited material for continuing studies e.g. to learn more about marker chromosome formation, or karyotypic evolution. To obtain information about their genetic content, in the present study we analyzed by FISH and multicolor-FISH approaches 19 sSMC cell lines obtained from the European Collection of Cell Cultures (ECACC). Microdissection and reverse painting, (sub-) centromere-specific multicolor-FISH (sub-)cenM-FISH, multicolor banding (MCB) and selected locus-specific FISH probes were applied. Thus, we were able to characterize comprehensively 14 out of 19 sSMC carrying cell lines; in the remaining five cases an sSMC could not be detected. Surprisingly, in six of the nine cell lines with sSMC previously characterized for their chromosomal origin by others, those results had to be revised. This has impact on the conclusions of previous studies, e.g. for uniparental disomy (UPD) in connection with sSMC.

Cell Line↗

PubMed2006

[Contribution of the study of evolution of major electrolytes contents in the aqueous humour by X-ray fluorescence and ICP/AES].

INTRODUCTION: In the scope of this study, we had to do a qualitative and quantitative research of the current electrolytes as part of aqueous humour samples taken from patients suffering from cataract. MATERIALS AND METHOD: The tests were carried out by X-ray fluorescence and ICP/AES. The detection limit for the electrolytes varied from 0.005 to 0.1 ppm. RESULTS: The test results show iron (minimum 0.82ppm; maximum 25.50ppm), copper (0.28ppm; 8.17ppm), brome (5.18 ppm ; 55.82ppm), zinc (0.70ppm ; 9.78ppm ), sodium (1274.83ppm, 5211.67 ppm), potassium (55.52ppm ; 255.02ppm), calcium (26.46 ppm ; 256.81ppm), magnesium (5.77ppm; 70.33ppm). CONCLUSION: The data study have enabled us to establish reference value for each electrolyte. Study of the comparative reference values, together with the contents found in the normal aqueous humour, the normal and pathologic crystalline lens, has shown a noticeably low concentration of electrolytes and breakdown of the sodium/potassium pump which ensures ionic exchange between aqueous humour and the crystalline lens.

Adult↗

PubMed2004

Selective deficits in the circadian light response in mice lacking PACAP.

Previous studies indicate that light information reaches the suprachiasmatic nucleus through a subpopulation of retinal ganglion cells that contain both glutamate and pituitary adenylyl cyclase-activating peptide (PACAP). Although the role of glutamate in this pathway has been well studied, the involvement of PACAP and its receptors is only beginning to be understood. To investigate the functions of PACAP in vivo, we developed a mouse model in which the gene coding for PACAP was disrupted by targeted homologous recombination. RIA was used to confirm a lack of detectable PACAP protein in these mice. PACAP-deficient mice exhibited significant impairment in the magnitude of the response to brief light exposures with both light-induced phase delays and advances of the circadian system impacted. This mutation equally impacted phase shifts induced by bright and dim light exposure. Despite these effects on phase shifting, the loss of PACAP had only limited effects on the generation of circadian oscillations, as measured by rhythms in wheel-running activity. Unlike melanopsin-deficient mice, the mice lacking PACAP exhibited no loss of function in the direct light-induced inhibition of locomotor activity, i.e., masking. Finally, the PACAP-deficient mice exhibited normal phase shifts in response to exposure to discrete dark treatments. The results reported here show that the loss of PACAP produced selective deficits in the light response of the circadian system.

Animals↗

PubMed2004

Follicular conjunctivitis caused by a mantle cell lymphoma.

BACKGROUND: Lymphoma of the conjunctiva as part of a systemic disease is rare. The follicular appearance of the lymphocyte hyperplasia may mimic the clinical picture of infectious or allergic conjunctivitis. We report on a case of marked chronic follicular conjunctivitis, finally diagnosed as mantle cell lymphoma. HISTORY AND SIGNS: A 52-year old male with a history of epiphora for one year, presented with follicular conjunctivitis in both eyes, a nodal mass in the upper right eyelid and nuchal lymphadenopathy. No infectious or allergic aetiology could be found. Conjunctival biopsy revealed a mantle cell lymphoma. Magnetic resonance tomography showed a bilateral spread into the orbital cavity. Other sites of involvement were the epipharynx and the cervical, axillary and paratracheal lymph nodes. THERAPY AND OUTCOME: Chemotherapy with hyper-CVAD (cyclophosphamide, vincristine, doxorubicine, dexamethasone) was initiated. After 4 of 6 cycles, all clinical tumour manifestations had disappeared completely. CONCLUSIONS: Conjunctival lymphoma may clinically resemble follicular conjunctivitis. Conjunctival biopsy may lead to early diagnosis and initiation of therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

The hierarchically organized splitting of chromosome bands into sub-bands analyzed by multicolor banding (MCB).

To clarify the nature of chromosome sub-bands in more detail, the multicolor banding (MCB) probe-set for chromosome 5 was hybridized to normal metaphase spreads of GTG band levels at approximately 850, approximately 550, approximately 400 and approximately 300. It could be observed that as the chromosomes became shorter, more of the initial 39 MCB pseudo-colors disappeared, ending with 18 MCB pseudo-colored bands at the approximately 300-band level. The hierarchically organized splitting of bands into sub-bands was analyzed by comparing the disappearance or appearance of pseudo-color bands of the four different band levels. The regions to split first are telomere-near, centromere-near and in 5q23-->q31, followed by 5p15, 5p14, and all GTG dark bands in 5q apart from 5q12 and 5q32 and finalized by sub-band building in 5p15.2, 5q21.2-->q21.3, 5q23.1 and 5q34. The direction of band splitting towards the centromere or the telomere could be assigned to each band separately. Pseudo-colors assigned to GTG-light bands were resistant to band splitting. These observations are in concordance with the recently proposed concept of chromosome region-specific protein swelling.

Chromosome Banding↗

PubMed2003

Involvement of the SREBP pathway in the mode of action of androgens in sebaceous glands in vivo.

Androgens have profound effects on the physiology of the sebaceous gland. Using the hamster ear sebaceous gland model, we performed a detailed kinetic study to clarify the mechanism of androgen action on sebaceous gland function. We demonstrated that the growth of sebaceous glands observed after androgen treatment was due to both an increase in sebocyte proliferation and a parallel induction of sebocyte terminal differentiation, as evidenced by the induction of the synthesis of specific sebaceous lipids such as cholesterol esters, triglycerides, and squalene. Accordingly, the effect of androgen treatment on the mRNA expression of several key enzymes involved in the synthesis of sebaceous lipids has been studied using semi-quantitative RT-PCR. Up-regulation by androgens of mRNA expression of HMG coenzyme A synthase and reductase, acetyl coenzyme A carboxylase (ACC), glycerol 3-phosphate acyl transferase (GPAT), and FAR-17c (stearoyl coenzyme A desaturase homologous), was demonstrated. Because sterol-response element(s) (SREs) are known to be present in the promoters of these genes, we analyzed the expression by RT-PCR and the activation of the transcription factor sterol regulatory element binding protein (SREBP) using immunoblotting experiments. Our results showed that SREBP-1 was up-regulated and rapidly activated after androgen treatment. Altogether, these results demonstrate for the first time that in sebaceous glands, in vivo, androgen regulates the synthesis of sebum lipids through the SREBP pathway.

Androgens↗

PubMed2002

FMRFamide modulates potassium currents in circadian pacemaker neurons of Bulla gouldiana.

The peptide FMRFamide (Phe-Met-Arg-Phe-NH(2)) is known to modulate the circadian pacemaker found in the eye of the marine snail Bulla gouldiana. In the present study, we investigated the cellular mechanisms underlying this modulation by examining the effects of FMRFamide on the membrane properties of the circadian pacemaker cells, known as basal retinal neurons in this preparation. Bath application of FMRFamide (0.1-1 microM) increased the membrane conductance, and hyperpolarized the membrane potential of these neurons. Next, perforated-patch recordings were used to demonstrate that FMRFamide reversibly increased the outward current amplitude due to an augmentation of a non-inactivating calcium-independent current. Reversal potential of the tail currents and its dependence on extracellular potassium concentration suggested potassium ions as the charge carrier for this current. The peptide-modulated outward current was blocked by 54% after bath application of the potassium channel blocker tetraethylammonium chloride and completely blocked by substituting cesium for intracellular potassium. Voltage dependence, activation kinetics and tail current kinetics of the FMRFamide-modulated current were consistent with values found for the delayed rectifier current.Overall, our data suggest that FMRFamide modulates a delayed rectifier potassium current and at least one other, less voltage-dependent conductance. This provides a mechanistic explanation for FMRFamide's ability to both shift the phase and attenuate light-induced phase shifts of the circadian pacemaker in B. gouldiana.

Action Potentials↗

PubMed2002

Demystifying chromosome preparation and the implications for the concept of chromosome condensation during mitosis.

The processes taking place during routine chromosome preparation are not well understood. In this study, the morphological changes in amniotic fluid cells, blood lymphocytes, and bone marrow cells in the metaphase stage were examined under an inverted microscope during chromosome preparation. The putative processes that occur during chromosome preparation were simulated in suspension, and the cells were treated with different mixtures of hypotonic solution, fixative, methanol, acetic acid, and water. Evaporation of the fixative was performed under normal atmospheric conditions and under vacuum at different levels of humidity. Freeze fracture electron microscopy was used to analyze the effects of fixative on the cell membrane. Confocal microscopic analysis was used to investigate three-dimensionally the effects of hypotonic treatment on the positions of chromosomes in fixed mitotic lymphocytes. Chromosome preparation-induced changes in the lengths of single chromosomes were also investigated. The results show that chromosome spreading involves significant water-induced swelling of mitotic cells during evaporation of the fixative from the slide, which is a prerequisite for chromosomal elongation, the production of metaphase spreads for chromosome analysis, and the appearance of Giemsa banding patterns. Hypotonic treatment is essential for well-spread metaphase chromosomes because it moves the chromosomes from a central to a more peripheral position in the cell, where they can be stretched more effectively during mitotic swelling. Like mitotic cells, isolated single chromosomes also have their own potential to swell and lengthen during chromosome preparation. We hypothesize that chromosome preparation leads to a genome-wide chromosomal region-specific opening of chromatin structures as GTG-light bands and sub-bands. Living cells may possess a similar mechanism, which is used only to open single chromatin structures to facilitate transcription. We propose the concept of chromosomal region-specific protein swelling.

Cells, Cultured↗

PubMed2002

[Genetic polymorphism of pyruvate dehydrogenase kinase 4 (PDK4), paraoxonase 2 (PON2), and fatty acid binding protein 2 (FABP2) in the NIDDM population of Senegal].

We reported a study about three candidate genes which may be involved in non-insulin dependent diabetes mellitus (NIDDM): Pyruvate Dehydrogenase Kinase 4 (PDK4), Paraoxonase 2 (PON2) and Fatty Acid Binding Protein 2 (FABP2). The reported mutation in the three candidate genes were tested for 179 black subjects from Dakar (Sénégal) by PCR-RFLP techniques. There was no significant difference between both control and NIDDM subjects. The genotype frequency in the senegalese population was quite similar as compared to reported frequency in white populations excepted for PDK4 polymorphism. These results suggest that none of these gene variants is a major NIDDM predisposing locus for the negroid population of Senegal.

Adolescent↗

PubMed2001

Activation-induced apoptosis and cell surface expression of Fas (CD95) ligand are reciprocally regulated by retinoic acid receptor alpha and gamma and involve nur77 in T cells.

It has been previously shown that CD4+ T cells enter the apoptotic suicide program via the Fas ligand (FasL)/Fas-mediated pathway upon T cell receptor (TCR) stimulation. In Jurkat cells TCR stimulation regulates the de novo synthesis of FasL, while in the influenza hemagglutinin-specific CD4+ murine T cell hybridoma (IP-12-7) the cell surface appearance of a preformed FasL is initiated. Both processes are dependent on new mRNA and protein synthesis, involve up-regulation of nur77, and can be inhibited by retinoic acids (RA). Two groups of nuclear receptors for RA have been identified: retinoic acid receptors (RAR) and retinoid X receptors (RXR). In this study various synthetic retinoids were used to define which receptors regulate TCR-mediated apoptosis. It is demonstrated that the inhibition is mediated via RARalpha, while RARgamma enhances TCR-mediated apoptosis, and when both receptors are stimulated, the costimulation by RXR will promote the effect of RARalpha. Evidence is presented that these receptors affect the transcriptional activity of nur77 and consequently the expression of FasL. Our data suggest a complex interaction between the various isoforms of retinoid receptors in regulating T cell death and demonstrate that the target through which retinoids regulate TCR-mediated apoptosis is nur77.

Apoptosis↗

PubMed2001

Differential diagnosis of prostate cancer and benign prostate hyperplasia using two-dimensional electrophoresis.

Prostate specific antigen (PSA) is a protease which is characteristic of the prostate. It is widely used as a serum marker for the early diagnosis of prostate cancer (PCa). Nevertheless, for concentrations between 4 and 10 ng/mL, PSA does not enable PCa to be distinguished from benign diseases, such as benign prostate hyperplasia (BPH). In sera, the use of a ratio between free PSA (PSA uncomplexed with protease inhibitor) and total PSA (free PSA and PSA bound to alpha-1 anti-chymotrypsin) enables the "gray zone" to be reduced, but an important proportion of patients are still wrongly classed. Using two-dimensional electrophoresis, we demonstrated using 52 PCa and 40 BPH well-documented clinical cases that BPH sera show a significantly greater percentage of low-molecular-weight free PSA elements (IwPSA) than PCa sera. In our study, the use of a ratio between IwPSA and standard free PSA enables the correct diagnosis of 100% of PCa and 82.5% of BPH cases as against when 73.1% and 42.5% respectively were correctly diagnozed using the total PSA and the free/total PSA ratio. This important finding may be related to differences in the mechanism secreting PSA from the prostate into the bloodstream. We have shown how a tissue marker may be turned into a powerful tumor marker by events probably unrelated to its expression.

Adult↗

PubMed2001

Limited cooperation between peroxisome proliferator-activated receptors and retinoid X receptor agonists in sebocyte growth and development.

We have found that sebaceous epithelial cell (sebocyte) differentiation is induced by cognate ligand-agonists of either peroxisome proliferator-activated receptors (PPARs) or retinoid X receptors (RXRs). In this study, we tested the hypothesis that PPAR-RXR cooperation is used in sebocytes as was reported to occur in gene transfection systems and liposarcoma cells through PPAR-RXR heterodimerization. PPAR agonists at maximally effective concentrations were tested in combination with a specific RXR agonist (the rexinoid CD2809) at doses ranging from submaximal to maximal in a primary rat preputial cell monolayer culture system. We evaluated ligand-agonists of PPARalpha (WY-14643 = WY), PPARgamma (troglitazone = TRO), and PPARdelta,alpha (carbaprostacyclin = cPGI2). Cell differentiation was determined by analysis of lipid staining and proliferation by cell counting. The RXR agonist induced a more diffuse and granular pattern of lipid staining throughout colonies than did PPAR agonists. The PPAR ligands WY, TRO, and cPGI2 induced 37, 35, and 59% lipid-forming colonies (LFCs), respectively (P < 0.05 vs controls, which averaged 19%). Low-dose rexinoid (10(-8) M) alone exerted no significant effect but amplified the effect of cPGI2 (P < 0.05). Middose rexinoid (10(-7) M), which alone induced about 40% LFCs, had an additive effect on differentiation with WY, TRO, and cPGI2 (71, 48, and 83% LFCs respectively, P < 0.05 vs each agonist alone). Proliferation was enhanced significantly by either rexinoid or cPGI2, but there was no change in growth when the two were added together. The greater effectiveness of cPGI2 than the other PPAR agonists may be explained by the predominance of PPARdelta gene expression in cultured sebocytes, as demonstrated by RNase protection assay. These studies demonstrate that a submaximal dose of RXR agonist augmented the stimulation of sebocyte differentiation by PPAR agonists, as expected from PPAR-RXR heterodimerization. However, the evidence for PPAR-RXR cooperativity is limited. The pattern of lipid staining is compatible with an independent effect of rexinoid on sebocyte differentiation. Furthermore, since there is no enhancement of the growth-promoting effects of RXR agonist and cPGI2 when they are combined, this effect also does not appear to be mediated by PPAR-RXR interaction.

Animals↗

PubMed2001

Adapalene biochemistry and the evolution of a new topical retinoid for treatment of acne.

The emergence of oral and topical retinoids was a major advance in the clinical management of acne vulgaris. However, the benefits of these agents were somewhat limited by the degree of side effects caused by these drugs. Over the last 15 years, researchers have sought compounds that can provide the manifold therapeutic benefits obtained with tretinoin and isotretinoin while minimizing the potential for irritation and other unwanted effects. Adapalene, a naphthoic-acid derivative, is one result of this search, and it serves as an example of rational drug development: the formulation of a novel substance with specific pharmacological properties and clinical objectives in mind. These goals included enhancing stability, enhancing anti-inflammatory effects, maintaining effectiveness and minimizing cutaneous irritation. This paper reviews the history of the development of adapalene, its unique physical and biochemical properties, and the pharmacological studies that demonstrate a wide range of retinoid-receptor, genetic and anti-inflammatory effects, all of which contribute to the therapeutic efficacy and improved tolerability of adapalene observed in the clinical use of this agent for the treatment of acne.

Acne Vulgaris↗

PubMed2001

An autocrine loop mediates expression of vascular endothelial growth factor in human dermal microvascular endothelial cells.

The expression of vascular endothelial growth factor mRNA and protein is regulated by a number of agents including growth factors, cytokines, and phorbol esters. Here we report that vascular endothelial growth factor is able to increase its own level in cultured human dermal microvascular endothelial cells. Accumulation of vascular endothelial growth factor mRNA and polypeptide can be detected as early as 4 h after addition of vascular endothelial growth factor to the cell culture medium. The autocrine action of vascular endothelial growth factor appears to be mediated by the KDR receptor. The increase of its own message by vascular endothelial growth factor is blocked by the transcription inhibitor actinomycin D. Transient transfection experiments performed with human dermal microvascular endothelial cells and using a 3.2 kb human vascular endothelial growth factor promoter fragment showed that vascular endothelial growth factor auto-induction can be mimicked at the promoter level. This indicates that the observed vascular endothelial growth factor mRNA increase after vascular endothelial growth factor treatment is occurring at the level of transcription. Furthermore, vascular endothelial growth factor auto-induction is inhibited by PD 098059, showing that phosphorylation events, catalyzed by mitogen activated protein kinases, are a prerequisite for the vascular endothelial growth factor effect. Examination of extracellular signal-regulated kinase and c-Jun N-terminal protein kinase catalytic activities showed that both enzymes have to be activated to mediate the vascular endothelial growth factor signal. Our data demonstrate for the first time the existence of an autocrine loop for vascular endothelial growth factor in endothelial cells. Most probably this represents an amplification mechanism for the action of vascular endothelial growth factor in the microvascularization process.

Autocrine Communication↗

PubMed2001

Cellular communication and coupling within the suprachiasmatic nucleus.

In mammals, the part of the nervous system responsible for most circadian behavior can be localized to a pair of structures in the hypothalamus known as the suprachiasmatic nucleus (SCN). Importantly, when SCN neurons are removed from the organism and maintained in a brain slice preparation, they continue to generate 24h rhythms in electrical activity, secretion, and gene expression. Previous studies suggest that the basic mechanism responsible for the generation of these rhythms is intrinsic to individual cells in the SCN. If we assume that individual cells in the SCN are competent circadian oscillators, it is obviously important to understand how these cells communicate and remain synchronized with each other. Cell-to-cell communication is clearly necessary for conveying inputs to and outputs from the SCN and may be involved in ensuring the high precision of the observed rhythm. In addition, there is a growing body of evidence that a number of systems-level phenomena could be dependent on the cellular communication between circadian pacemaker neurons. It is not yet known how this cellular synchronization occurs, but it is likely that more than one of the already proposed mechanisms is utilized. The purpose of this review is to summarize briefly the possible mechanisms by which the oscillatory cells in the SCN communicate with each other.

Animals↗

PubMed2001

Analysis of prostate specific antigen and alpha1-antichymotrypsin interaction using antipeptide monoclonal antibodies.

PURPOSE: The synthetic peptides E30D and D10P that correspond to prostate specific antigen (PSA) sequences 60-91 and 78-89, respectively, and contain the kallikrein loop were used to immunize mice to obtain anti-PSA monoclonal antibodies (mAbs). MATERIALS AND METHODS: Antipeptide mAb characteristics were studied using biosensor technology and enzyme-linked immunosorbent assay, and analyzing the mAb effects on PSA-alpha1-antichymotrypsin (ACT) complex formation and PSA enzymatic activity. Epitope mapping of these mAbs was performed using overlapping peptide synthesis on nitrocellulose membrane. RESULTS: Anti-E30D mAbs bound PSA coated on the solid phase only, whereas anti-D10P mAbs recognized PSA in detection as well as in capture. However, these mAbs appeared to be anti-total PSA mAbs. Anti-E30D and anti-D10P mAbs were directed against linear epitopes corresponding to residues H74-Y77 and N84-R88, respectively, of the PSA sequence. Anti-D10P mAb recognition of PSA and PSA-ACT complex was equimolar, although an existing molecular model suggested that the sequence corresponding to anti-D10P mAb epitope was involved in the interaction site of PSA with ACT. Furthermore, we were unable to inhibit the enzymatic activity of PSA as well as PSA-ACT complex formation. Finally, the epitope N84-R88 overlapped the cleavage site R85-F86 of PSA. CONCLUSIONS: The linear anti-D10P mAb epitope is located outside of the PSA-ACT binding site. However, these mAbs may be of value for evaluating the presence of different molecular PSA forms in sera.

Animals↗