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See detailHuman kininogens of low and high molecular mass: quantification by radioimmunoassay and determination of reference values.
Adam, Albert; Albert, Adelin ULg; Calay, G et al

in Clinical Chemistry (1985), 31(3), 423-6

Kininogens of low and high molecular mass, highly purified from human plasma, were used to raise antisera in rabbits. To obtain immunologically intact tracers, we labeled the kininogens by the lodogen ... [more ▼]

Kininogens of low and high molecular mass, highly purified from human plasma, were used to raise antisera in rabbits. To obtain immunologically intact tracers, we labeled the kininogens by the lodogen method, followed by double chromatography, first on Sephadex G50 and then on Sephadex G200 for high-molecular-mass kininogen or on G100 for low-molecular-mass kininogen. Both assays are sensitive, accurate, and reproducible. On an equimolar basis, the high-molecular-mass kininogen cross reacted completely in the determination of low-molecular-mass analyte. Moreover, the radioimmunoassay for the former was highly specific. After optimizing the time and temperature of incubation to provide rapid and reliable results, we determined 95% reference intervals from a large sample of healthy subjects (250 men, 200 women): 109-272 and 69-116 mg/L for the low- and high-molecular-mass kininogens, respectively. [less ▲]

See detailHuman lysozyme amyloidosis
Dumoulin, Mireille ULg; Johnson, Russell J.K.; Bellotti, Vittorio et al

in Uversky, V.; Fink, A. L. (Eds.) Protein Misfolding, Aggregation and Conformational Diseases. II. Molecular Basis of Conformational Diseases. (2007)

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See detailHuman Muscle Energetics During Voluntary and Electrically Induced Isometric Contractions as Measured by 31p Nmr Spectroscopy
Vanderthommen, Marc ULg; Gilles, R.; Carlier, Pierre ULg et al

in International Journal of Sports Medicine (1999), 20(5), 279-83

Electrical stimulation (ES) and voluntary contraction (VC) were compared in the quadriceps muscle of ten male volunteers. In both modes, a workload corresponding to 20% of maximal voluntary contraction ... [more ▼]

Electrical stimulation (ES) and voluntary contraction (VC) were compared in the quadriceps muscle of ten male volunteers. In both modes, a workload corresponding to 20% of maximal voluntary contraction was applied during 64 isometric contraction (5.5 s)-relaxation (5.5 s) cycles. The protocols were performed in a 1.5 T whole-body magnet. The Pi/PCr ratio and the intracellular pH (pHi) were monitored by 31P NMR spectroscopy during baseline, exercise and recovery periods, in a superficial region of the vastus medialis. During baseline, the Pi/PCr ratio (0.12 vs. 0.10) and the pHi (7.01 vs. 7.00) were comparable in both conditions. During exercise, the Pi/PCr ratio was higher (0.36 vs. 0.14) and the pHi was lower (6.85 vs. 7.07) during ES than during VC. For the same external work production, these results reflect a different metabolic solicitation in the ES quadriceps than in the VC ones. [less ▲]

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See detailHuman muscle proteome modifications after acute or repeated eccentric exercises
Hody, Stéphanie ULg; Leprince, Pierre ULg; Sergeant, K. et al

in Medicine & Science in Sports & Exercise (2011), 43(12), 2281-2296

INTRODUCTION:: DOMS (Delayed-Onset Muscle Soreness), a condition triggered by eccentric exercise, affects muscle cells at a biochemical level in a poorly understood fashion. The objective of the present ... [more ▼]

INTRODUCTION:: DOMS (Delayed-Onset Muscle Soreness), a condition triggered by eccentric exercise, affects muscle cells at a biochemical level in a poorly understood fashion. The objective of the present study was to examine human muscle proteome modifications induced by strenuous eccentric exercises following a specific training aimed to prevent DOMS. METHODS:: Biopsy of the rectus femoris were taken from healthy human volunteers in three successive conditions: (1) at rest, (2) 24 hours after an injuring exercise protocol consisting of 3 series of 30 maximal contractions of the quadriceps on an isokinetic dynamometer, (3) 24 hours after a similar exercise bout preceded either by 5 eccentric training sessions, or no training. RESULTS:: Muscle damage was assessed before and 1 day after each maximal eccentric test by comparing three indirect markers: plasma activity of creatine kinase (CK), muscle stiffness and subjective pain intensity. Compared to the first eccentric test, those markers were reduced after the second test and further reduced if this second test followed the eccentric training, thus confirming the protective effect of such training. Muscle protein extracts were subjected to a 2D-DIGE proteomic analysis coupled with MALDI-TOF-MS protein identification. Surprisingly, we observed that myosin heavy chains decreased after the first eccentric test, and were reduced further with other contractile proteins after the second test. Furthermore, the expression of several glycolytic enzymes decreased only after the second test that was preceded by a specific training. CONCLUSION:: These findings suggest that the eccentric training resulted in a switch to oxidative metabolism, which may be associated with protection from DOMS. [less ▲]

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See detailHuman papillomavirus 16 virus-like particles use heparan sulfates to bind dendritic cells and colocalize with langerin in Langerhans cells.
Bousarghin, Latifa; Hubert, Pascale ULg; Franzen, Elisabeth et al

in Journal of General Virology (The) (2005), 86(Pt 5), 1297-305

Langerhans cells (LC), the immature dendritic cells (DC) that reside in epithelial tissues are among the first immune cells to encounter human papillomavirus (HPV) and are not activated by HPV virus-like ... [more ▼]

Langerhans cells (LC), the immature dendritic cells (DC) that reside in epithelial tissues are among the first immune cells to encounter human papillomavirus (HPV) and are not activated by HPV virus-like particles (VLPs) in contrast to DC. The notion that the differences in response to HPV VLPs between LC and DC are associated with different types of cell binding and intracellular trafficking has been addressed. Inhibition experiments with heparin and sodium chlorate showed that heparan sulfates are necessary for HPV 16 VLPs to bind to DC but not to LC. Electron microscopy analysis demonstrated a colocalization of HPV 16 VLPs and langerin, which is expressed only by LC. This colocalization was observed on the cell surface but also in cytoplasmic vesicles. As anti-langerin antibodies, HPV 16 VLPs were associated with a faster entry kinetics in LC, as reflected by the fact that VLPs were observed near the nuclear membrane of LC within 10 min whereas more than 60 min were needed in DC. However, no difference between LC and DC was observed for the endocytosis pathway. HPV 16 VLPs entered in both DC and LC by a clathrin-dependent-pathway and were then localized in large cytoplasmic vesicles resembling endosomes. [less ▲]

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See detailHuman papillomavirus capsids trigger crosstalk between dendritic and NK cells
Langers, Inge ULg; Renoux, Virginie; Pirotte, Evelyne et al

Poster (2012, September 26)

The immune system controls, at least partially, human papillomavirus (HPV) infection and subsequent tumour development as demonstrated by a higher tumour prevalence in immunodeficient patients. More than ... [more ▼]

The immune system controls, at least partially, human papillomavirus (HPV) infection and subsequent tumour development as demonstrated by a higher tumour prevalence in immunodeficient patients. More than 90% of HPV-infected women will clear the virus within two years. However, it remains unclear which immune cells are implicated in this process and although dendritic cells (DC) and NK cells play a key role in host resistance to virus and tumour, no study has been performed evaluating their crosstalk in this context. Virus-like particles (VLP) formed by the HPV major capsid protein L1 are licensed as vaccine against cervical cancer and we have recently shown that NK cells can directly interact with these HPV-VLP [1]. Here, we investigated the impact of this activation on NK-DC crosstalk. Interestingly, NK cells increase DC maturation induced by HPV-VLP as shown by an up-regulation of HLA-DR and CD86 on DC. Transwell experiments indicated that the expression of HLA-DR is cell-cell contact and soluble factor dependent, whereas only soluble factors seem to be required for CD86 expression. Moreover, in the presence of HPV-VLP and NK cells, DC produce higher amounts of IL12p70, while the production of the immunosuppressive cytokine IL10 remains unchanged. We also demonstrated that DC can up-regulate the expression of NK activation markers (CD69 and HLA-DR) in the presence of HPV-VLP. This up-regulation requires both cell-cell contact and soluble factors. Regarding HLA-DR marker, the increased expression on CD56bright cells is mediated by soluble factors, whereas cell-cell contacts are also important for HLA-DR expression on CD56dim cells. In the presence of DC activated by HPV-VLP, the function of NK cells is also modified since they become more cytotoxic against HPV+ cell line and secrete more IFN-γ. Our results suggest that NK-DC crosstalk could play a role in the immune response induced by HPV-VLP during vaccination protocols against cervical cancer. [less ▲]

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See detailHuman papillomavirus DNA strongly correlates with a poorer prognosis in oral cavity carcinoma.
Duray, A; Descamps, G; Decaestecker, C et al

in Laryngoscope (2012), 122(7), 1558-65

OBJECTIVES/HYPOTHESIS: The prevalence of human papillomavirus (HPV) in a clinical series of 162 patients with oral squamous cell carcinoma (OSCC) was studied. Furthermore, we analyzed the correlation ... [more ▼]

OBJECTIVES/HYPOTHESIS: The prevalence of human papillomavirus (HPV) in a clinical series of 162 patients with oral squamous cell carcinoma (OSCC) was studied. Furthermore, we analyzed the correlation between the immunohistochemical expression of p16, p53, epidermal growth factor receptor (EGFR), and HPV status to predict survival in OSCC patients. STUDY DESIGN: Retrospective study. METHODS: Paraffin-embedded samples from OSCC patients (n = 162) were evaluated for the presence of HPV DNA using both GP5+/GP6+ consensus polymerase chain reaction (PCR) and type-specific E6/E7 PCR to detect HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, and 68. Immunohistochemical staining for p16, p53, and EGFR was also performed. RESULTS: The type-specific E6/E7 PCR demonstrated that 65 of the 147 OSCC patients (44%) presented with high-risk (hr) HPV types and that 38 of the 147 OSCC patients (26%) presented with low-risk (lr) HPV types. Comparable p53 and EGFR expression levels were observed in the hr HPV+ group (41.5% p53+, 92% EGFR+) and the lr HPV+ group (57% p53+, 92% EGFR+). Conversely, a slight increase in the proportion of p16+ tumors was observed in the hr HPV+ group (65%) compared with the lr HPV+ group (44%). In regard to patient outcome, the presence of HPV was correlated with a worse prognosis (P = .007). CONCLUSIONS: A high prevalence of hr and lr HPV infections was detected in the OSCC patients included in the study. Moreover, hr HPV positivity was correlated with a decreased 5-year disease-free survival rate compared with HPV- and lr HPV+. [less ▲]

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See detailHuman papillomavirus entry into NK cells requires CD16 expression and triggers cytotoxic activity and cytokine secretion
Renoux, Virginie; Bisig, Bettina; Langers, Inge ULg et al

Poster (2013, May)

Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV ... [more ▼]

Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV-infected women clear the virus within two years. However, it remains unclear which immune cells are implicated in this process and no study has evaluated the direct interaction between HPVs and NK cells, a key player in host resistance to viruses and tumors. We demonstrated an NK-cell infiltration in HPV- associated preneoplastic cervical lesions. Since HPVs cannot grow in vitro, virus-like particles (VLPs) were used as a model for studying the NK-cell response against the virus. Interestingly, NK cells displayed higher cytotoxic activity and cytokine production (TNF-a and IFN-g) in the presence of HPV-VLPs. Using flow cytometry and microscopy, we observed that NK-cell stimulation was linked to rapid VLP entry into these cells by macropinocytosis. Using CD16+ and CD16- NK-cell lines and a CD16-blocking antibody, we demonstrated that CD16 is necessary for HPV–VLP internalization, as well as for degranulation and cytokine production. Thus, we show for the first time that NK cells interact with HPVs and can participate in the immune response against HPV-induced lesions. [less ▲]

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See detailHuman papillomavirus entry into NK cells requires CD16 expression and triggers cytotoxic activity and cytokine secretion.
Renoux, Virginie; Langers, Inge; Dortu, Estelle et al

Conference (2013, January 28)

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See detailHuman papillomavirus entry into NK cells requires CD16 expression and triggers cytotoxic activity and cytokine secretion.
Renoux, Virginie ULg; Bisig, Bettina ULg; Langers, Inge ULg et al

in European journal of immunology (2011), 41(11), 3240-3252

Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV ... [more ▼]

Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV-infected women clear the virus within two years. However, it remains unclear which immune cells are implicated in this process and no study has evaluated the direct interaction between HPVs and NK cells, a key player in host resistance to viruses and tumors. We demonstrated an NK cell infiltration in HPV-associated pre-neoplastic cervical lesions. Since HPVs cannot grow in vitro, virus-like particles (VLPs) were used as a model for studying the NK cell response against the virus. Interestingly, NK cells displayed higher cytotoxic activity and cytokine production (TNF-alpha and IFN-gamma) in the presence of HPV-VLPs. Using flow cytometry and microscopy we observed that NK cell stimulation was linked to rapid VLP entry into these cells by macropinocytosis. Using CD16(+) and CD16(-) NK cell lines and a CD16-blocking antibody, we demonstrated that CD16 is necessary for HPV-VLP internalization, as well as for degranulation and cytokine production. Thus, we show for the first time that NK cells interact with HPVs and can participate in the immune response against HPV-induced lesions. [less ▲]

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See detailHuman papillomavirus predicts the outcome following concomitant chemoradiotherapy in patients with head and neck squamous cell carcinomas.
Duray, Anaelle; Descamps, Geraldine; Decaestecker, Christine et al

in Oncology Reports (2013), 30(1), 371-6

We investigated the prevalence of human papillomavirus (HPV) in a clinical series of 72 patients with head and neck squamous cell carcinoma (HNSCC) using a retrospective and prospective study design. The ... [more ▼]

We investigated the prevalence of human papillomavirus (HPV) in a clinical series of 72 patients with head and neck squamous cell carcinoma (HNSCC) using a retrospective and prospective study design. The majority of patients were smokers and/or drinkers and were treated with concomitant chemoradiotherapy (CCR). Furthermore, we assessed the impact of HPV positivity on the response to CCR. Paraffin-embedded samples from HNSCC patients (n=72) were evaluated for the presence of HPV DNA using both GP5+/GP6+ consensus PCR and type-specific E6/E7 PCR to detect HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67 and 68. The type-specific E6/E7 PCR demonstrated that 20 out of 69 HNSCC patients (29%) presented with high-risk (HR) HPV types and that 5 of the 69 HNSCC patients (7%) presented with low-risk (LR) HPV types. Using the GP5+/GP6+ PCR, we observed that the rate of response was statistically lower in the HPV+ group (P=0.02). Concerning patient outcomes in terms of recurrence and survival, we observed that the prognosis was poorer for HPV+ patients. We showed for the first time that patients with HPV+ HNSCC present with a worse prognosis after CCR. This observation highlights the need for prospective studies with large numbers of patients and a detailed history of tobacco and alcohol consumption before validating HPV as a marker of prognosis following CCR. [less ▲]

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See detailHuman papillomavirus type 33 upstream regulatory elements can control gene expression in human cervical keratinocytes
Lauricella-Lefèbvre, M. A.; Rentier, Bernard ULg; Piette, Jacques ULg

in Archives Internationales de Physiologie, de Biochimie et de Biophysique (1992), 100

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See detailHuman Papillomavirus Virus-Like particles and NK cell interactions:role of CD16
Renoux, Virginie ULg; Langers Inge; Clémenceau Béatrice et al

in International Immunology (2010), 22(suppl Pt 5), 17

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See detailHuman papillomavirus, lichen sclerosus and penile cancer: A study in Belgium.
D'Hauwers, K. W. M.; Depuydt, C. E.; Bogers, J. J. et al

in Vaccine (2012), 30(46), 6573-7

PURPOSE: The prevalence of penile cancer varies between 1.5 (industrialized countries) and 4.5 per 100,000 men (non-industrialized countries). Predominant histological subtype is squamous cell carcinoma ... [more ▼]

PURPOSE: The prevalence of penile cancer varies between 1.5 (industrialized countries) and 4.5 per 100,000 men (non-industrialized countries). Predominant histological subtype is squamous cell carcinoma (SCC). Human papillomavirus (HPV) is found in 40-46% of cases: penile cancer is considered to behave as vulvar cancer. Non HPV related risk factors are lack of circumcision, phimosis, chronic inflammation, and smoking. The role of lichen sclerosus (LS) is unclear. Clinical diagnosis is difficult and treatment often mutilating. Preventive measures can be taken since the risk factors are known: the use of the prophylactic HPV vaccines may contribute. We measured the prevalence of HPV and LS in penile cancer in Belgium. MATERIALS AND METHODS: We found 76 samples of penile lesions in the archives of the departments of Histology of four university hospitals in Belgium. Real-time PCR of type-specific HPV DNA was performed targeting 18 HPV types. PRINCIPAL RESULTS: Patients with penile intraepithelial neoplasia (PeIN) were 56.1 years of age: patients with invasive penile cancer (IPC) 68.5 (p=0.009). Fifty-five samples (55/76) were adequate for HPV targeting. Overall HPV DNA was 70.9%: 89.5% in samples of PeIN (n=19) and 61.1% in samples of IPC (n=36). Invasive penile cancer samples were less likely to be HPV infected (p=0.028). HPV 16 was most prevalent: 48.3%: 20% PeIN, and 28.3% IPC. HPV DNA of the types, included in the prophylactic vaccines, was found in 33% of PeIN and 31.7% of IPC samples. Thrice, low risk HPV (lrHPV) types 6 (1 IPC) and 11 (1 PeIN, 1 IPC) were solely present. There was no difference in the presence of LS between HPV positive and HPV negative samples (p=0.944). CONCLUSIONS: Prevalence of HPV DNA in penile lesions in Belgium is high. However, the prophylactic vaccines may contribute to primary prevention of only a subset of cases. The role of LS remains unclear. [less ▲]

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See detailThe human PDZome: a gateway to PDZ mediated functions.
Belotti, Edwige; Polanowska, Jolanta; Daulat, Avais M. et al

in Molecular & Cellular Proteomics (in press)

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See detailThe Human Placenta Becomes Haemochorial at the 13th Week of Pregnancy
Foidart, Jean-Michel ULg; Hustin, Jean-Michel; Dubois, Michel ULg et al

in International Journal of Developmental Biology (1992), 36(3), 451-3

Histological specimens of recent implantation sites are the basis of our current concept on human embryo implantation and placental development. In the Carnegie Collection maternal red blood cells were ... [more ▼]

Histological specimens of recent implantation sites are the basis of our current concept on human embryo implantation and placental development. In the Carnegie Collection maternal red blood cells were detected early in the primitive intervillous space (10th-12th day after conception). These cells were localized to the trophoblastic lacunae and originated from distended peripheral maternal sinusoids (Kaufmann, 1981). The classical theory states that progressively more and more maternal vessels are tapped. A true maternal blood flow is established around the 29th day. Dynamic investigations of human placental development in vivo are scarce and hampered by ethical considerations and the absolute requirement to refrain from using non aggressive and potentially harmful techniques. Despite these limitations such studies provide new insights that surprisingly contradict our previously and seemingly definitely established knowledge of the early phases of placental vascularization, and lead us to conclude that there is an absence of maternal blood circulation in the intervillous placental space (IVS) during the 12 first weeks of human pregnancy. [less ▲]

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See detailHuman placental GH is found neither in amniotic fluid and fetal serum nor in pituitary GH-secreting adenoma.
Frankenne, d; Beckers, Albert ULg; El Khayat, N. et al

Conference (1987)

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