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H Bittard

Publications and source records attributed to H Bittard.

At least 19 recordsLinked to original sources
PubMed2006

Intravenous apoptotic spleen cell infusion induces a TGF-beta-dependent regulatory T-cell expansion.

Apoptotic leukocytes are endowed with immunomodulatory properties that can be used to enhance hematopoietic engraftment and prevent graft-versus-host disease (GvHD). This apoptotic cell-induced tolerogenic effect is mediated by host macrophages and not recipient dendritic cells or donor phagocytes present in the bone marrow graft as evidenced by selective cell depletion and trafficking experiments. Furthermore, apoptotic cell infusion is associated with TGF-beta-dependent donor CD4+CD25+ T-cell expansion. Such cells have a regulatory phenotype (CD62L(high) and intracellular CTLA-4+), express high levels of forkhead-box transcription factor p3 (Foxp3) mRNA and exert ex vivo suppressive activity through a cell-to-cell contact mechanism. In vivo CD25 depletion after apoptotic cell infusion prevents the apoptotic cell-induced beneficial effects on engraftment and GvHD occurrence. This highlights the role of regulatory T cells in the tolerogenic effect of apoptotic cell infusion. This novel association between apoptosis and regulatory T-cell expansion may also contribute to preventing deleterious autoimmune responses during normal turnover.

Adoptive Transfer↗
PubMed2004

T-cell flow-cytometry crossmatch and long-term renal graft survival.

Flow cytometry crossmatch (FCXM) is a more sensitive technique than classical complement-dependent cytotoxicity (CDC) for the detection of donor-directed antibody before renal transplantation. Nevertheless, the role of FCXM in predicting long-term survival of kidney grafts is still unclear. The purpose of our study was to evaluate the impact of a positive T-cell FCXM (T-FCXM) on long-term kidney allografts outcome. Of the 184 consecutive kidney transplantations performed in our center between 1 January1991 and 15 November 1996 a FCXM, performed concurrently to the pre-transplant CDCXM, was available for 170 patients. The CDCXM was negative in all recipients. Among these recipients, 12 (7.1%) had a positive T-FCXM. These patients were not different from patients with a negative T-FCXM for donor and recipient age, sex, frequency of second transplantation, number of human leukocyte antigen matches or mismatches. Frequency of immunized patients was higher in kidney recipients with a positive FCXM (58.3% vs. 24.7%; p=0.02, chi-square test). Survival analysis revealed that kidney graft outcome was better in negative T-FCXM recipients (p=0.03), while patient survival was not statistically different. Our results suggest that a positive pre-transplant T-FCXM despite a negative CDCXM is associated with an impaired long-term graft survival in renal allotransplantation.

Age Factors↗
PubMed2003

Detection of the human papillomavirus and analysis of the TP53 polymorphism of exon 4 at codon 72 in penile squamous cell carcinomas.

Human papillomaviruses (HPV) are thought to be involved in penile squamous cell carcinomas (SCC). A common polymorphism at codon 72 of exon 4 encoding either arginine (Arg) or proline (Pro) has been shown to affect HPV-mediated degradation of p53 in vitro, and may represent a risk factor for HPV-induced carcinogenesis. The presence of HPV DNA as well as the TP53 polymorphism at codon 72 of exon 4 were investigated in a series of 45 penile SCC. HPV detection and typing were carried out by polymerase chain reaction (PCR) with generic primers (MY09-MY11 and FAP59-FAP64), and type-specific DNA probes. TP53 polymorphism was further investigated using Denaturing Gradient Gel Electrophoresis (DGGE). HPV DNA was detected in 67% of penile SCC and 32% of benign lesions (BL) (P<0.05). Among the TP53 amplified samples, the rate of Arg homozygosity in penile SCC was 61% compared with 68% in BL (non-significant (NS)). Our results demonstrate a strong association between penile SCC and the presence of HPV DNA. The TP53 Arg/Arg genotype does not appear to represent a risk factor for the development of genital SCC in men, and no correlation was found between the TP53 polymorphism at codon 72 and the presence of HPV DNA.

Adult↗
PubMed2002

Absence of anti-Müllerian hormone (AMH) and M2A immunoreactivities in Sertoli cell-only syndrome and maturation arrest with and without AZF microdeletions.

BACKGROUND: Some genes identified in the AZF locus are expressed only in germinal cells; others are ubiquitous. AZF microdeletions seem to occur at the earliest stages of ontogenetic development, and one might therefore assume that Sertoli cells preserve some immature characteristics and that their immunophenotype may be modified by the existence of a molecular defect. MATERIALS AND METHODS: Two immunohistological markers of Sertoli cell immaturity [anti-Müllerian hormone (AMH) and M2A] were tested in two histopathological groups (maturation arrest at spermatocyte I stage and Sertoli cell-only syndrome). We analysed 68 testicular samples obtained from 39 patients with non-obstructive azoospermia associated or not with AZF microdeletions. RESULTS: The absence of M2A and AMH immunoreactivity in adult gonads was observed without any correlation to spermatogenetic impairment or molecular deficit in the AZF region. In the samples of these two series, Sertoli cells showed a mature phenotype for AMH and M2A markers. CONCLUSIONS: In patients with AZF microdeletions, the genotype-phenotype correlations seem to be more complex than has been suggested previously; more detailed characterization of the immunohistochemical phenotype associated with the molecular defect may be useful in understanding the spermatogenic failure mechanism.

Adult↗
PubMed2002

Variants of renal angiomyolipoma closely simulating renal cell carcinoma: difficulties in the histological diagnosis.

Renal angiomyolipoma is considered to be a benign renal tumor composed of atypical blood vessels, smooth muscles and fat cells. We report 2 cases of unilateral renal angiomyolipoma. In both cases, our preoperative diagnosis was renal cell carcinoma, because no low density area compatible with fat tissue was noted in the tumors on radiographic evaluation. Through histological examination, both tumors proved to be angiomyolipomas mainly composed of epithelioid cells in 1 case, and spindle-shaped smooth muscle cells mimicking a leiomyoma in the other case. Both patients are well showing no evidence of metastases 16 and 14 months after nephrectomy, respectively.

Angiomyolipoma↗
PubMed2001

Relationship between expansion of the CAG repeat in exon 1 of the androgen receptor gene and idiopathic male infertility.

OBJECTIVE: To determine whether expansion of CAG repeats in exon 1 of the androgen receptor is correlated with impaired spermatogenesis in patients with male idiopathic infertility. DESIGN: A retrospective study. SETTING: Medical school in Besançon, France. PARTICIPANT(S): Thirty-seven infertile patients with azoospermia or oligospermia and 50 fertile controls. INTERVENTION(S): History, physical, hormonal assays, semen analysis, and collection of blood samples in order to study the androgen receptor's gene. MAIN OUTCOME MEASURE(S): Blood samples were collected from each infertile patient and control. The length of the CAG repeat segment was evaluated by using polymerase chain reaction (PCR) electrophoresis in exon 1 and PCR single-strand conformation polymorphism in exons 2-8. RESULT(S): The mean length of the CAG repeats was significantly different between infertile and fertile patients (23.91 +/- 0.5 vs. 22.20 +/- 0.4). No mutation was detected in exons 2-8 of the androgen receptor gene in infertile patients. CONCLUSION(S): Expansion of the CAG repeat segment of the androgen receptor is correlated with male idiopathic infertility. The number of CAG repeats may therefore have a modulatory effect on normal androgen receptor function.

Adult↗
PubMed2001

Protein kinase C signalling pathway is involved in the regulation of vascular endothelial growth factor expression in human bladder transitional carcinoma cells.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor associated with the growth and metastasis of various cancers and plays a prominent role in vesical angiogenesis regulation. In this study, we investigated the effect of the phorbol 12-myristate 13-acetate (PMA) on the expression of VEGF in human bladder transitional carcinoma cells (RT4). RT4 cells expressed three VEGF isoforms (VEGF(189), VEGF(165), VEGF(121)). PMA increased VEGF mRNA expression time-dependently with a peak at 4 h. PMA increased the half-life of VEGF mRNA. The amount of VEGF protein in conditioned media was increased by PMA in a dose-dependent manner with a maximal effect at 10(-7) M. Staurosporine and calphostin C (PKC inhibitors) decreased PMA-induced VEGF mRNA expression as opposed to protein kinase A or cyclic nucleotide-dependent protein kinase inhibitors. Thus, in RT4 cells, VEGF expression is up-regulated by PMA via the PKC signalling pathway and according to a posttranscriptional mechanism.

Carcinoma, Transitional Cell↗
PubMed2001

The predictive value of muscularis mucosae invasion and p53 over expression on progression of stage T1 bladder carcinoma.

PURPOSE: We determine the significance of muscularis mucosae invasion and nuclear p53 over expression on the progression of stage T1 transitional cell bladder cancer. MATERIALS AND METHODS: The pathological findings in 149 cases of T1 tumors diagnosed between 1973 and 1996 were reviewed. Diagnosis was stage T1 in 94 tumors in which the muscular layer was clearly identifiable and disease-free. Mean followup was 64.9 months (range 5 to 288). T1 bladder cancers were subclassified into 2 groups, with (T1b) or without (T1a) muscularis mucosae invasion. The p53 nuclear antibody immunoreactivity was determined with antibody D07 and a cutoff point at 15%. RESULTS: T1 subclassification was possible in all 94 patients. Of all tumors 37.2% expressed p53 nuclear over expression. Univariate statistical analysis showed that p53 expression (p <0.05) and tumor invasion depth (p <0.001) significantly correlated with progression. However, on multivariate analysis only invasion depth (p <0.0001) and associated carcinoma in situ (p <0.03) remained independently significant as predictors of progression. CONCLUSIONS: In our study the depth of tumor invasion was a significant independent predictor of progression in patients with T1 bladder cancer. This result suggests that the depth of invasion in stage T1 should be included in the histopathological report.

Aged↗
PubMed2001

[Spontaneous thrombosis of left varicocele].

Spontaneous thrombosis of a varicocele is a rare event and difficult to diagnose, as the clinical symptoms during the acute phase can simulate torsion of the spermatic cord or strangulated inguinal hernia leading to a useless surgical exploration. The authors report a case of spontaneous thrombosis of a varicocele which was diagnosed clinically, allowing conservative medical treatment.

Adult↗
PubMed2001

[Usefulness of p53 in the clinical management of bladder tumors].

The antioncogene p53 has been the subject of many studies in the field of bladder cancer, for many years and there appears to be a good correlation between p53 protein overexpression and pejorative clinicopathological factors, but contradictory results have been reported concerning its prognostic value. These discordances can be partly explained by the various immunohistochemical methods used in published series. Standardization of a highly sensitive and specific immunohistochemical method for the detection of p53 alterations now appears to be essential in order to accurately determine the value of p53 in the clinical management of bladder cancer.

Autoantibodies↗
PubMed2001

[Angiogenesis in bladder: prognosis indicator and therapeutic target].

Angiogenesis is a complex, multi-step process which leads to the formation of new blood capillaries (neovessels) from preexisting vessels. It is essential top the growth of solid tumours and tumour metastasis (tumour angiogenesis). This process is initiated by the synthesis, by tumour cells and non-malignant tumour-associated cells, of growth factors called antigenic factors or inducers. bFGF (basic Fibroblast Growth Factor) and VEGF (Vascular Endothelial Growth Factor) are the two angiogenic factors involved in bladder tumour angiogenesis. The angiogenic activity of a bladder tumour can be measured by the microvascular density (MVD), considered by some authors to be an independent prognostic indicator of recurrence and survival in the group of invasive bladder tumours. VEGF expression in bladder tumours and biological fluids (serum, urine) appears to be a predictive marker of the risk of progression of superficial bladder tumours. Urinary bFGF assay reveals high levels in patients with bladder tumour, but this elevation is not specific to bladder tumours. Inhibition of tumour angiogenesis has become a therapeutic target. Intravesical suramine and a fumagillin analogue (TNP-470) have given promising results in terms of efficacy and safety in the treatment of bladder tumours.

Endothelial Growth Factors↗
PubMed2001

[Testicular trauma: report of 56 cases].

OBJECTIVES: To assess the diagnostic value of clinical examination and ultrasound in testicular trauma and to analyse the complications of the various treatments proposed (surgical and medical treatments), in order to more clearly define the place of medical treatment in this form of trauma in young adults. PATIENTS AND METHODS: 56 cases of testicular trauma in 50 patients were managed between January 1990 and January 2000. In the absence of clinical and ultrasonographic criteria of severity (haematocele, very large intratesticular haematoma, rupture of the tunica albuginea), medical treatment consisting of rest, anti-inflammatory drugs, and testicular support was instituted. Surgical exploration was performed when serious lesions of the testis were suspected. Three subgroup were defined: the medical treatment subgroup, the early surgical treatment subgroup, and the deferred surgical treatment subgroup (more than 3 days after trauma). The immediate morbidity and long-term sequelae were analysed in each of these three subgroups. RESULTS: The clinical features of pain and scrotal swelling make assessment of the lesions difficult. Testicular ultrasound can help the clinician, but it has a low sensitivity for the diagnosis of testicular rupture. No significant difference was observed between the three subgroups in terms of morbidity, orchidectomy, and long-term sequelae rates. CONCLUSION: In the absence of signs of severity, medical treatment with regular surveillance remains justified. However, in the case of doubtful clinical or ultrasound findings, surgical exploration must be performed as soon as possible.

Adolescent↗
PubMed2001

Serum levels of vascular endothelial growth factor as a prognostic factor in bladder cancer.

PURPOSE: Vascular endothelial growth factor is an overriding growth factor mediating tumor angiogenesis. We correlated serum vascular endothelial growth factor in patients with bladder cancer with clinical parameters. MATERIALS AND METHODS: Serum vascular endothelial growth factor in 58 patients with bladder cancer, including superficial and invasive tumors in 42 and 16, respectively, and 41 healthy controls was measured by sandwich enzyme immunoassay. RESULTS: Significant differences in serum vascular endothelial growth factor were observed in healthy controls and patients with bladder cancer (mean 248 versus 100 pg./ml., p <0.001). The serum level was significantly associated with tumor stage (p <0.0001), grade (p <0.002), vascular invasion (p <0.001) and carcinoma in situ (p <0.01). Patients with metastasis had a significantly higher levels than those with localized diseases (mean 582 versus 194 pg./ml., p <0.0001). At a cut-off of 400 pg./ml. the sensitivity and specificity of the test for differentiating patients with and without metastatic diseases was 87.5% and 98%, respectively (p <0.0001). Univariate statistical analysis showed that an increase in serum vascular endothelial growth factor level greater than 400 pg./ml. was significantly related to disease-free survival. On multivariate analysis only stage remained as an independent prognostic factor. CONCLUSIONS: Although vascular endothelial growth factor did not remain an independent prognostic factor on multivariate analysis, our data indicate that the level of vascular endothelial growth factor may be a valuable angiogenic marker for identifying metastatic bladder cancer. It may be used as a new predictor of disease.

Adult↗
PubMed2001

[Idiopathic male infertility and androgen receptors].

In France, 12 to 15% of couples experience procreation difficulties. A disorder of spermatogenesis (oligospermia, azoospermia) is responsible in 1/3 of cases. These forms of infertility, labelled idiopathic, probably have a genetic component, like microdeletions of the Y chromosome. The normal rate of circulating androgens suggests the implication, in some cases, of an abnormality from the receptor to the androgens (RA) of these male infertilities, whose number remains to be defined. Point mutations on exons of the gene encoding the AR cannot account for all cases of infertility due to idiopathic disorders of spermatogenesis. Expansion of the number of CAG triplets of exon 1 of the AR gene, already demonstrated in a fatal degenerative neuropathy (Kennedy's disease, in which more than 50% of patients are infertile), has been detected in these cases of idiopathic infertility and would be responsible for AR dysfunction. The number of these triplets is also decreased in patients with androgen-dependent prostate cancer. The polymorphism of repetition of CAG triplets would therefore be responsible for fine adjustment of the AR between excessive and insufficient function. ICSI. (Intra-Cytoplasmic Sperm Injection) is currently proposed in these cases of infertility, but the consequences of transmission of these abnormalities to the offspring are unknown.

Humans↗
PubMed2000

[Malignant penile melanoma].

The authors report the case of a very large, obstructive malignant melanoma (MM.) of the prepuce, encasing all of the distal extremity of the penis, and discovered at a late metastatic stage (regional lymph node metastasis). Palliative treatment, consisting of partial penectomy associated with a complementary induction and maintenance chemotherapy did not achieve any objective response at one year. MM. of the penis are rare urological tumours, including MM of the penis and MM of the male urethra (exclusively mucosal involvement). The diagnosis of MM of the penis must be considered in any case of black or brown lesion of the glans, which is the most frequent site. The prognosis is determined by the clinical stage (BRACKEN and DIOKNO classification) and by the depth and level of tumour invasion (BRESLOW index and CLARK's degree of dermal invasion). The 5-year survival is inversely proportional to the tumour thickness. The treatment of MM of the penis is surgical; the extent of resection and the indication for lymph node dissection depend on the patient's age, sexuality, and the stage of the disease and depth of tumour invasion.

Humans↗
PubMed2000

[Spermatic cord torsion in adults].

OBJECTIVES: The objective of this retrospective study, conducted between January 1988 and December 1998, was to demonstrate that physical examination is sufficient to manage patients with torsion of the spermatic cord. MATERIAL AND METHODS: 72 patients, admitted with an empirical diagnosis of torsion of the spermatic cord based on physical examination, underwent emergency surgery via a scrotal incision. Orchidopexy was performed when the surgical diagnosis was in favour of torsion. We classified our series into 2 groups according to the presence or absence of torsion and we defined two subgroups in the torsion group: the orchidectomy subgroup and the non-orchidectomy subgroup. RESULTS: The suspicion of torsion of the spermatic cord was confirmed in 70.8% of cases. No mortality or morbidity were observed for wrongly operated patients. The study of the sensitivity (Se) and positive predictive value (PPV) of clinical signs defined a group of men requiring emergency surgical exploration: men presenting with scrotal pain in the absence of any urinary signs (Se = 98%, PPV = 72%), negative urinary dip-stick (Se = 97%, PPV = 71%), with pain described as violent (Se = 80%, PPV = 76%), an ascended testis (Se = 62%, PPV = 86%) and a subacute stage (Se = 68%, PPV = 79%). The only pejorative factor detected in the presence of testicular necrosis was a delay before management greater than 6 hours. The length of hospital stay (p < 0.041) and the complication rate (p < 0.023) were greater in the orchidectomy subgroup compared to the non-orchidectomy subgroup. CONCLUSION: This retrospective study confirms that physical examination is sufficient to ensure good management of torsion of the spermatic cord in adults and that emergency surgical exploration is justified at the slightest doubt.

Adult↗