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Biomedical subjects

J C Noël

Publications and source records attributed to J C Noël.

At least 19 recordsLinked to original sources

Bilateral extensive vascular calcification of the breast associated with coagulative necrosis: a calciphylaxis-like syndrome.

A case of asynchronous bilateral breast necrosis in a 40-year-old woman with untreated chronic hypercholesteraemia is described. Mastectomies were performed, and histological examination revealed bilateral breast calciphylaxis characterized by extensive vascular calcification with coagulative necrosis. Breast calciphylaxis is a rare disease clinically characterized by progressive tissular necrosis with secondary cutaneous ulceration and by vascular calcification and thrombosis. However, the nature of the vascular calcification has remained poorly understood up to now, owing to the absence of any precise mineralogical examination. In this case the mineral deposits were analysed for the first time: only hydroxyapatite was found. The etiology is discussed, and the high cholesterol rate of the patient is implicated.

Adult↗

Cervical response to vaccination against HPV16 E7 in case of severe dysplasia.

OBJECTIVE: To evaluate the tolerance to vaccination against human papillomavirus (HPV)16 E7 (in SB adjuvant ASO2B) and its histological and immunohistological effects on HPV16 associated high-grade cervical dysplasias associated with HPV16. STUDY DESIGN: Five patients with histologically demonstrated severe cervical dysplasia (CIN3) HPV16 positive were injected three times before conization was performed 2 months after the first injection. We studied cytological, histological, proliferative pattern and immune profile before and after vaccination. The slides were compared with those obtained from non-injected patients. RESULTS: The injections were well tolerated and the specimens displayed a limited regression of the lesions. Nevertheless, massive CD4 and CD8 T cell lymphocytic infiltration was noticed after vaccination. DISCUSSION: We conclude that the vaccination we used provides an obvious immune histological reaction in the HPV infected cervix and that the 2 months delay before the final step (conization) is done is probably too short.

Adolescent↗

Ki-67 immunostaining activity is higher in positive axillary lymph nodes than in the primary breast tumor.

BACKGROUND: The monoclonal antibody Ki-67 allows to investigate the proliferative activity of tumor and is a clinically useful marker to characterize breast cancer. In this study, we have compared Ki-67 activity in 38 primary breast tumors and in their respective positive axillary lymph nodes (ALNs). METHODS: Immunohistochemistry with the monoclonal antibody against Ki-67 was performed in 38 nodes positive breast carcinomas and in their respective positive ALNs. Statistical analysis was performed with the Student's t-test (2-tailed) for equality of means. RESULTS: The proliferation index measured by Ki-67 expression was significatively higher (p < 0.02) in ALN than in the primary tumor (29.8% v.s. 21.8%). CONCLUSION: These results strongly suggest a higher proliferation and perhaps aggressivity of metastatic neoplastic cells when compared with their respective primary tumor. Perhaps, in the future, these differences in proliferation behavior might be taken into account when considering the choice of the adjuvant therapy.

Adult↗

Multiple HPV-positive basal cell carcinomas on the abdomen in a young pregnant woman.

Basal cell carcinoma (BCC) is the most common malignant skin tumour. In the last few years, the incidence of multiple BCC has also increased in young patients. We describe the clinical case of a young 29-year-old woman who developed 7 BCC on her abdomen during her first pregnancy and 4 other similar tumours 2 years later during her second pregnancy, all located on the abdomen. Polymerase chain reaction revealed the presence of numerous human papillomavirus DNA sequences. To our knowledge, such a clinical presentation has not been previously reported. Different physiopathological considerations are discussed.

Basal Cell Carcinoma↗

[The pathology department].

The evolution of the Laboratory of Pathology at Erasmus Hospital is directly related to the morphological diagnosis integration in the medico-surgical organization of the Hospital. Such integration is based on the creation of links between the Laboratory of Pathology and the clinical departments and necessitates permanent adaptations to new complementary technology. Immunohistochemical methods were gradually included in the surgical morphological diagnosis. Currently, new markers from molecular biology are needed to obtain accurate pathological diagnosis. We observe an increasing hyperspecialization of the morphological classification with complete integration of such biological markers leading to the necessity of carrying out collegial diagnosis. The development of the telepathology technology permits international collegial diagnosis. According to its central position the Laboratory of Pathology plays an important part in the development of the clinical and fundamental research. The research subjects of the Laboratory of Pathology concern diagnostic and prognostic evaluation in colic cancers, sarcomas, brain tumors and HPV related tumors endometriosis.

Belgium↗

Phase II double-blind, placebo-controlled study of the safety and efficacy of cidofovir topical gel for the treatment of patients with human papillomavirus infection.

Genital condylomata acuminata are nonmalignant human papillomavirus (HPV)-induced tumors in which HPV types 6 and 11 are most commonly found. Usual treatments for condylomata acuminata are nonspecific and are based on the destruction or removal of infected tissue. These procedures are often painful and are characterized by a high relapse rate. We report here what is to our knowledge the first double-blind, placebo-controlled study of the use of cidofovir, a nucleotide analogue, for the treatment of genital papillomavirus infections. Thirty patients were enrolled in the study; 19 received cidofovir, and 11 received placebo. The median number of warts and the median baseline wart area were comparable for both groups. Nine (47%) of 19 patients in the cidofovir group had a complete response (total healing), compared with 0 of the patients in the placebo group (P=.006). None of the patients in the cidofovir group experienced progression of the disease, compared with 5 (45%) of 11 patients in the placebo group. The side effects recorded for both groups were comparable.

Adult↗

Warty carcinoma of the anus: a variant of squamous cell carcinoma associated with anal intraepithelial neoplasia and human papillomavirus infection.

Warty carcinoma (WC) is a rare variant of squamous cell carcinoma primarily described in the vulva in younger women and classically associated with human papillomavirus (HPV) infection. The gross findings are similar to those of verrucous carcinoma with large, exophytic tumors with a papillomatous surface. Microscopically, the tumor is papillated and contains fibrovascular cores covered by hyperkeratotic epithelium showing presence of koilocytes. We report a case of anal squamous cell carcinoma showing similar features, occurring in a young immunosuppressed male patient with a history of multifocal anal intraepithelial neoplasia (AIN). HPV-16 has been demonstrated both in the WC and in adjacent AIN, but the HPV status appears different in the two lesions: integrated in WC and episomal in AIN lesions. We also have demonstrated by immunohistochemistry that both WC and AIN are highly proliferative entities sharing the same MIB-1 pattern, and that WAF1/CIP1 protein expression is common in the two lesions irrespective of p53 protein expression.

Adult↗

Overexpression of 27-kDa heat shock protein relates to poor histological differentiation in human oesophageal squamous cell carcinoma.

AIMS: Various stress conditions such as heat, chemical and mechanical stresses are known to play a major role in oesophageal squamous cell carcinoma development. Our goal was to evaluate whether changes in stress-induced 27-kDa heat shock protein (HSP27) expression could be demonstrated during oesophageal carcinogenesis. METHODS AND RESULTS: HSP27 expression was studied using immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections from 21 oesophageal squamous cell carcinomas occurring in smokers and/or alcohol abusers. Oesophagus from healthy patients (controls) (five), chemical (eight) and infectious oesophagitis (six) were also included in the study. In normal oesophagus, the protein is present only in the upper epithelial layers. In contrast, in chemical or infectious oesophagitis its expression is strong and occurs in all the epithelial layers including the basal layer. In non-tumoral oesophageal mucosa from smoking and/or drinking patients adjacent to invasive carcinoma, the distribution of the protein is patchy and irregular. In malignant areas, HSP27 protein expression increases drastically from dysplastic lesions to invasive carcinoma, being highest in the less differentiated areas. CONCLUSIONS: In human oesophagus, HSP27 expression is induced by various stresses but alcohol and tobacco generate focal perturbations in the stress response. Tumour immunoreactivity for this protein increases with the anaplasia of the tumour, as in some other tumours in which it is considered to play a role in drug resistance. To our knowledge, these data have not been previously described for oesophageal squamous cell carcinoma.

Carcinoma, Squamous Cell↗

Does prostaglandin E1 therapy modify the intracavernous musculature?

PURPOSE: Intracavernous injection of prostaglandin E1 in patients with erectile dysfunction has become widespread. However, to our knowledge long-term side effects on the penile smooth muscles in man have not been documented. We evaluated the histological changes of intracavernous smooth muscle after long-term treatment with prostaglandin E1. MATERIALS AND METHODS: A total of 10 patients with a mean age of 56.5 years (range 46 to 69) underwent biopsy of the corpora before (5) and after (10 in both corpora) prostaglandin E1 treatment. Between 150 and 250 injections during 3 years were performed, and the dosage varied from 5 to 20 microg. Only 1 patient injected prostaglandin E1 on both sides. Staining with hematoxylin and eosin, and immunohistochemical staining with actin anti-actin of intracavernous smooth muscle and its quantification with computerized image analysis were performed. RESULTS: No histological difference was observed with classic staining. A reduction was noted in the percentage of intracavernous smooth muscle after treatment in 2 of 5 patients on the side of injection (before 35% and 41%, and after 19% and 30%, respectively) but there was no difference with the other corpus cavernosum. No difference was observed in the percentage of intracavernous smooth muscle between both corpora in the 5 patients with biopsies performed only after treatment. CONCLUSIONS: Prostaglandin E1 does not seem to alter intracavernous structures.

Aged↗

IL-5 mediates eosinophilic rejection of MHC class II-disparate skin allografts in mice.

CD4 T cells play a crucial role in the acute rejection of MHC class II-disparate skin allografts, mainly by Fas/Fas ligand-mediated cytotoxicity. Because recent observations indicate that eosinophils may be found within allografts rejected by CD4 T cells, we evaluated the role played by IL-5, the main eosinophil growth factor, and by eosinophils in the rejection of MHC class II-disparate skin grafts. C57BL/6 mice rapidly rejected MHC class II-disparate bm12 skin grafts. Rejected skins contained a dense, aggressive eosinophil infiltrate. Lymphocytes isolated from lymph nodes draining rejected bm12 skin were primed for IL-5 secretion, and IL-5 mRNA was present within rejected grafts. The IL-5/eosinophil pathway played an effector role in allograft destruction, because the rejection of bm12 skin was significantly delayed in IL-5-deficient mice as compared with wild-type animals. The role of the IL-5/eosinophil pathway was further investigated in MHC class II-disparate donor-recipient strains unable to establish Fas/Fas ligand interactions. Fas ligand-deficient gld/gld mice rejected bm12 skins, and bm12 mice rejected Fas-deficient lpr/lpr C57BL/6 skins. Neutralization of IL-5 prevented acute rejection in both combinations. We conclude that MHC class II-disparate skin allografts trigger an IL-5-dependent infiltration of eosinophils that is sufficient to result in acute graft destruction.

Acute Disease↗

Evaluation of the role of genital human papillomavirus in the pathogenesis of ungual squamous cell carcinoma.

Human papillomaviruses (HPV), and particularly HPV 16, have been associated with ungual squamous cell carcinoma (USCC). But their role in tumor development remains unclear. In genital carcinoma, where the oncogenic role of HPV is well established, integration of HPV DNA into the host cell genome seems to be important for malignant transformation. To clarify the issue, we have studied the physical state of HPV 16 in 3 cases of in situ USCC by the polymerase chain reaction and by in situ hybridization. HPV DNA was integrated into the human genome in 2 cases and episomal in 1 case. This particular physical state of HPV 16 in USCC, similar to those encountered in anogenital SCC, confirms the probable role of this kind of virus in the pathogenesis of USCC.

Aged↗

Critical roles for IL-4, IL-5, and eosinophils in chronic skin allograft rejection.

C57BL/6 mice injected with the 145-2C11 anti-CD3 mAb and grafted with MHC class II disparate bm12 skin develop a chronic rejection characterized by interstitial dermal fibrosis, a marked eosinophil infiltrate, and an obliterative intimal vasculopathy. Because these changes occur in the absence of alloreactive antibodies, we examined the contribution of cytokines in their pathogenesis. Chronically rejected grafts showed a marked accumulation of both IL-4 and IL-5 mRNA. Mixed lymphocyte reaction experiments established that mice undergoing chronic rejection were primed for IL-4, IL-5, and IL-10 secretion. In vivo administration of anti-IL-4 mAb completely prevented allograft vasculopathy as well as graft eosinophil infiltration and dermal fibrosis. Injection of anti-IL-5 mAb or the use of IL-5-deficient mice as recipients also resulted in the lack of eosinophil infiltration or dermal fibrosis, but these mice did develop allograft vasculopathy. Administration of anti-IL-10 mAb did not influence any histologic parameter of chronic rejection. Thus, in this model, IL-4- and IL-5-mediated tissue allograft eosinophil infiltration is associated with interstitial fibrosis. IL-4, but not eosinophils, is also required for the development of obliterative graft arteriolopathy.

Animals↗

Chronic rejection of major histocompatibility complex class II-disparate skin grafts after anti-CD3 therapy: a model of antibody-independent transplant vasculopathy.

BACKGROUND: Chronic rejection remains a leading cause of allograft loss. Histologically, it is characterized by arterial intimal thickening and parenchymal fibrosis. The immune mechanisms triggering chronic rejection are still uncompletely understood. METHODS: We performed major histocompatibility complex (MHC) class H-incompatible skin grafts from C-H2bm12 (bm12, H2bm12) into C57BL/6 (C57BL/6, H2b) recipients immunosuppressed with a short course of anti-CD3 monoclonal antibodies to prevent acute rejection. RESULTS: More than 80% of grafts survived for prolonged periods, but eventually all displayed macroscopic and microscopic evidence of chronic rejection. At histology, there was a progressive arterial intimal thickening as well as intense dermal fibrosis. This was accompanied by an inflammatory infiltrate consisting of lymphocytes and macrophages, but also of a considerable number of eosinophils. Mice with chronic rejection were unable to generate anti-donor MHC class II cytotoxic T lymphocyte activity at either 20 or 60 days after transplant. Furthermore, transplantation of bm12 skins on C57BL/6-congenic, Ig knock-out mice was associated with the development of a chronic rejection that was identical to that occurring in wild-type C57BL/6 animals, indicating that alloantibodies are not necessary in this model. CONCLUSIONS: (1) Skin grafts may undergo chronic rejection with the characteristic lesions of vasculopathy and fibrosis; (2) chronic rejection of MHC class II-disparate skins may occur in the absence of direct cytotoxic T lymphocyte activity or alloantibodies.

Animals↗