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Biomedical subjects

I Fayt

Publications and source records attributed to I Fayt.

At least 19 recordsLinked to original sources

Evidence of human papilloma virus infection but lack of Epstein-Barr virus in lymphoepithelioma-like carcinoma of uterine cervix: report of two cases and review of the literature.

Lymphoepithelioma-like carcinoma (LELC) of uterine cervix is an uncommon variant of squamous cell carcinoma (SCC). We report here 2 new cases in which DNA sequences from human papilloma virus (HPV) types 16 and 18 were detected by polymerase chain reaction (PCR). To the best of our knowledge, HPV infection has not been previously described in similar cases occuring in European women. Moreover, Epstein-Barr virus (EBV), which is frequently associated with cervical LELC in Asian women, was absent in our 2 cases. These results suggest that HPVs but not EBV can play a role in the pathogenesis of LELC occuring in women originating from Western countries.

Carcinoma, Squamous Cell↗

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↗

Smooth muscles are frequent components of endometriotic lesions.

Deep infiltrating endometriosis (deeper than 5 mm under the peritoneum) often takes the form of a nodular lesion (or 'adenomyotic nodule') consisting of smooth muscles and fibrosis with active glands and scanty stroma. Thus, among endometriotic lesions, a certain distinction is drawn between musculo-glandular lesions and glandular lesions composed of endometrial-like epithelium surrounded by a cell-producing (cytogenous) stroma. The aim of this study was to detect by immunohistochemistry, with a monoclonal antibody against muscle-specific actin, the presence of smooth muscles in 54 endometriotic lesions originating from four different pelvic locations (peritoneum, ovary, rectovaginal septum and uterosacral ligaments) and to quantify the smooth muscle content. Smooth muscles were frequent components of endometriotic lesions in pelvic locations. In addition, smooth muscles were significantly (P < 0. 001) more abundant in endometriotic lesions than in their respective unaffected sites. This finding supports, at least partially, the occurrence of a metaplastic phenomenon in the pathogenesis of endometriotic lesions. The definition of distinct endometriotic entities based on the difference in the tissue composition of the lesions (endometriotic nodules versus adenomyotic nodules) is inconsistent with the very frequent presence of smooth muscle cells in endometriosis irrespective of its localization.

Actins↗

Sigmoid endometriosis and ovarian stimulation.

In-vitro fertilization (IVF) and ovarian stimulation are frequently performed in patients with endometriosis. Although endometriosis is a hormone-dependent disease, the rate of IVF complications related to endometriosis is low. We report four cases of severe digestive complications due to the rapid growth of sigmoid endometriosis under ovarian stimulation. In three patients, sigmoid endometriosis was diagnosed at laparoscopy for sterility. Because of the absence of digestive symptoms or repercussion on the bowel, no bowel resection was performed before ovarian stimulation. All patients experienced severe digestive symptoms during ovarian stimulation, and a segmental sigmoid resection had to be performed. Analysis of endoscopic and radiological data demonstrated that bowel lesions of small size may rapidly enlarge and become highly symptomatic under ovarian stimulation. At immunohistochemistry, these infiltrating lesions displayed high populations of steroid receptors and a high proliferative index (Ki-67 activity), suggesting a strong dependence on circulating ovarian hormones and a potential for rapid growth under supraphysiological oestrogen concentrations. Clinicians should be aware of this rare but severe digestive complication of ovarian stimulation. The early diagnosis of such lesions may help the patients to avoid months of morbidity falsely attributed to ovarian stimulation side effects. Further experience is necessary to determine the optimal attitude when diagnosing a small and asymptomatic endometriotic bowel lesion before ovarian stimulation.

Adult↗

Relationship between endometriotic foci and nerves in rectovaginal endometriotic nodules.

The histological relationships between fibrotic tissue, endometriotic foci and nerves in the rectovaginal septum endometriotic or adenomyotic nodule were studied. This is considered to be one of the most severe forms of deep endometriosis. Masson's trichrome staining for fibrosis detection and immunohistochemistry with the S100 monoclonal antibody for nerve detection were performed in 28 rectovaginal endometriotic nodules from patients presenting with severe dysmenorrhoea and deep dyspareunia (23 patients with no other endometriotic location or potential cause of pain at laparoscopy and ultrasonography; five patients with multiple pelvic endometriotic localizations and other potential causes of pain at laparoscopy). Patients were allocated to two groups on the basis of their preoperative pain scores for pelvic pain, dysmenorrhoea and deep dyspareunia (group 1, score >7; group 2, score < or =7). For each symptom, the mean number of nerves and endometriotic lesions per high-power field and the mean largest diameter of the lesions were not statistically different in groups 1 and 2. The mean percentages of nerves located within the fibrosis of the nodule and within endometriotic lesions were significantly higher in group 1 than in group 2. Among nerves located within endometriotic lesions, there was a significantly higher proportion showing intraneurial and perineurial invasion by endometriosis in group 1 than in group 2. In rectovaginal endometriotic nodules, there was a close histological relationship between nerves and endometriotic foci, and between nerves and the fibrotic component of the nodule. We postulate that such topographical relationships could at least partially explain the strong association between this lesion and pain.

Adult↗

Penile intraepithelial neoplasia overlying Kaposi's sarcoma lesions: role of viral synergy?

Several viral agents have been detected in the lesional tissue of Kaposi's sarcoma (KS). Their precise oncogenic role remains to be determined. A 32-year-old heterosexual man with acquired immunodeficiency syndrome (AIDS) who had penile lesions of KS with overlying epithelial changes characteristic of intraepithelial neoplasia associated with concurrent infection by human papillomavirus (HPV) and human herpesvirus 8 (HHV-8) is reported. The absence of viral DNA from uninvolved skin suggests that this coinfection is more than coincidental and may involve synergy between these viruses, as has already been suggested for HPV and herpes simplex 2 virus.

Acquired Immunodeficiency Syndrome↗

Correlation and prognostic significance of p53, p21WAF1/CIP1 and Ki-67 expression in patients with superficial bladder tumors treated with bacillus Calmette-Guerin intravesical therapy.

PURPOSE: We determine if, before intravesical bacillus-Calmette Guerin (BCG) therapy, p53, p21WAF-1-CIP1 (a critical downstream effector of p53 pathway of cell growth control, inhibiting cyclin dependent kinases) and the cell proliferation marker Ki-67 (MIB-1) could be used as prognostic markers of response to BCG in patients with superficial bladder tumors. MATERIALS AND METHODS: The study included 47 patients with superficial bladder tumors at high risk for recurrence or progression treated with 6 weekly intravesical BCG instillations. We analyzed p53, p21 and Ki-67 on paraffin embedded samples by immunohistochemistry and the percentage of positive cells was determined in a blinded fashion. Quantitative immunostaining was analyzed in relation to time to recurrence and progression using univariate or multivariate analysis and the Kaplan-Meier method. RESULTS: During a mean followup of 24.6 months 23 of the 47 patients (48.9%) presented with tumor recurrence and 10 (21.2%) had later progression to invasive disease. A p21 over expression (greater than 10%) was observed in 23 tumors (48.9%) and positively correlated with p53 (p = 0.0097) but not with Ki-67 (p = 0.327). Of the tumors 18 (38.2%) were p53 and p21 negative. Among p21 positive tumors 15 (65.2%) were p53 and p21 positive, suggesting that p21 may also be regulated by p53 independent pathways. However, p53 did not act as a predictor of recurrence or progression. In contrast, using Kaplan-Meier curves p21 over expression (greater than 10%) and Ki-67 at a 25% cutoff were associated with shorter recurrence-free survival (both p = 0.02 log rank test) but they did not predict additional information about risk of progression. However, multivariate analysis failed to demonstrate any independent prognostic value for p21 or Ki-67 in contrast to tumor stage. CONCLUSIONS: Our results indicate that p21WAF-1-CIP1 seems to be regulated by p53 independent pathways in superficial bladder cancer. The present study did not indicate an independent prognostic significance in patients treated with BCG for p53, p21WAF-1-CIP1 or Ki-67 markers. Larger prospective studies are needed to evaluate further the independent value of these biological markers in superficial bladder cancer management.

Adjuvants, Immunologic↗

Pre-Kaposi's sarcoma: an expansion of the spectrum of Kaposi's sarcoma lesions.

We report on a lymphoedematous form of classic Kaposi's sarcoma (KS) in which characteristic purplish lesions were surrounded by atypical oedematous, flesh-coloured papules. Histological examination of these papular lesions revealed a proliferation of grouped, rather thick-walled capillaries with inflammatory infiltrates. Hot-start PCR amplification with KS 330-233 primer sequences demonstrated the presence of human herpesvirus 8 (HHV-8) sequences. In addition, cells isolated from these oedematous papules showed morphological and immunohistochemical features similar to those reported for KS-derived spindle cells. As a whole, these results suggest that these oedematous papular lesions represent pre-KS lesions and may expand the clinico-pathological spectrum of KS. The role of oedema in their induction is discussed.

Aged↗

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↗

PCR assay fails to detect molluscum contagiosum virus-related sequences in AIDS-related Kaposi's sarcoma.

Previous PCR-based studies have demonstrated the presence of various viral DNA or RNA sequences in Kaposi's sarcoma (KS) tissues. To date, only human herpesvirus 8 (HHV-8) DNA sequences are found consistently in KS. The putative role of this agent in KS pathogenesis remains, however, to be determined; HHV-8 could infect populations endemically and could be reactivated in patients with KS. A close association between AIDS-related KS and molluscum contagiosum occurrence was found and this study was conducted primarily to search for the presence of molluscum contagiosum virus DNA sequences in KS. Frozen KS samples were examined for the presence of both HHV-8 and molluscum contagiosum virus DNA sequences by PCR. Despite a high rate of co-infection, no molluscum contagiosum virus (MCV) DNA sequence could be found in the KS samples whereas HHV-8 was uniformly detected. These results suggest that the high prevalence of MCV in AIDS patients with KS relies on a mode of transmission common for HHV-8 and molluscum contagiosum virus rather than on a multiviral etiology of KS. They may also indicate a particular susceptibility of the host to viral reactivation. If this is so, the failure to detect MCV DNA sequences in KS tissues by PCR indicates that locally produced or released cyotokines are not involved in the latter process.

AIDS-Related Opportunistic Infections↗

Detection and identification of human papilloma viral DNA, types 16, 18, and 33, by a combination of polymerase chain reaction and a colorimetric solid phase capture hybridisation assay.

A colorimetric microplate hybridization assay was developed previously to simplify detection procedures of DNA fragments resulting from polymerase chain reactions (PCR). This format has now been adapted for the simultaneous detection and identification of three human papillomavirus (HPV), types 16, 18 and 33, associated frequently with cervical cancer. This post-PCR detection system uses three type-specific capture oligonucleotides linked covalently to a single microplate well and three type-specific multibiotinylated oligonucleotidic probes for detection. It therefore offers a double specificity; the first is conferred by pairs of primers, specific of each type of virus tested, and the second, by the sets of capture and detection probes which are complementary to internal regions of the amplified DNA fragments. The detection format outperformed agarose gel electrophoresis of amplified DNA products in sensitivity and specificity. The rapidity and simplicity of this hybridisation system would justify its use in routine diagnostic examination of cervical specimens (smears and biopsies).

Colorimetry↗

Herpesvirus-like DNA sequences and Kaposi's sarcoma: relationship with epidemiology, clinical spectrum, and histologic features.

BACKGROUND: The evidence of an infectious agent other than human immunodeficiency virus (HIV) acting as a possible etiologic cause of Kaposi's sarcoma (KS) has received considerable attention in the last years. Recently, DNA sequences from a new herpesvirus (HHV-8) have been observed in several cases of KS. The discovery suggests that this virus may play a role in the pathogenesis of KS. To evaluate these results, we determined the frequency of HHV-8 DNA sequences in 78 specimens of KS according to different epidemiologic origins (sporadic KS: 6, immunosuppressive drug-associated: 11, and AIDS-associated: 61), clinical forms (cutaneous: 69, mucocutaneous: 4 and visceral; 5) and histologic variants (early-patch: 40, late-plaque or nodular: 38). METHODS: We used the hot start polymerase chain reaction amplification method with KS330 primers specific for HHV-8 DNA. Tumoral or nontumoral skins and visceral specimens free of KS, originating from patients with KS positive for HHV-8 DNA sequences or from immunosuppressed patients without KS, served as controls. Normal skin from healthy HIV seronegative patients was also included. RESULTS: HHV-8 DNA sequences were found in 3 of the 6 sporadic KS (50%), in 5 of the 11 immunosuppressive drug-associated KS (45%), in 41 of the 61 AIDS-associated KS (67%), in 32 of the 69 cutaneous KS (46%), in 3 of the 4 mucocutaneous KS (75%) in 2 of the 5 systemic KS (40%), in 23 of the 40 early or patchstage KS (58%), in 30 of the 38 late plaque or nodular stages KS (79%). These sequences were also demonstrated in one sample of skin with scabies and in a glomerulonephritis lesion from two immunosuppressed patients with KS who were also positive for herpesvirus-like in their KS lesions. None of the other skin or visceral specimens, originating from healthy, AIDS, or transplanted patients without KS, were positive. CONCLUSIONS: Our results reinforce the hypothesis that HHV-8 is incriminated in different epidemiologic, clinical and histologic stages of KS and could contribute to the pathogenesis of this tumor. However, the presence of HHV-8 DNA sequences in skin and visceral samples free of KS from KS indicates that the virus is not restricted to the tumor tissue, and thus is able to disseminate in many organs of the target individual. Absence of the virus from healthy, AIDS, or transplanted patients without KS suggests that the viral Sequences either do not spread easily or do not easily maintain themselves in the human population.

Acquired Immunodeficiency Syndrome↗

p53 Protein overexpression in verrucous carcinoma of the skin.

BACKGROUND: Verrucous carcinoma is a rare variant of well-differentiated squamous cell carcinoma which is characterized by a marked local aggressivity and a poor metastatic potential. Until now, little has been known about the oncogenic mechanisms of this tumor. Recently, extensive investigations have shown that p53 protein, a nuclear protein with oncogene-suppressing activity, may play a crucial role in cell transformation and immunoreactivity for this protein is found in a wide variety of cancers. OBJECTIVE AND METHODS: The aim of the present study is to examine the frequency of immunohistochemically detectable p53 protein by using two monoclonal antibodies (D07 and BP53-12) in 8 cases of formalin-fixed and paraffin-embedded specimens of verrucous skin carcinoma. RESULTS: Overexpression of p53 protein was detected in 6 (75%) of the cases examined with the D07 antibody and in 5 (62.5%) cases with BP53-12. The p53 positivity was shown in a peripheral distribution affecting mainly the basal cell layers of tumoral islands. CONCLUSION: In a high percentage of verrucous carcinoma, p53 immunoreactivity has not been previously described in the literature and our findings suggest that abnormal expression of p53 tumor suppressor protein is a common event in the pathogenesis of this tumor.

Aged↗

Proliferating cell nuclear antigen distribution in verrucous carcinoma of the skin.

Verrucous carcinoma (VC) of the skin is a rare variety of well-differentiated squamous cell carcinoma (SCC) characterized by aggressive local growth and a low metastatic potential. These tumours are known to have histological and virological features similar to classic warts or condylomata. The aim of the present study was to map the proliferative compartment in VC (n = 7) in comparison with warts (n = 10) and typical well-differentiated SCC (n = 10). The proliferating cells were detected by immunostaining of proliferating cell nuclear antigen (PCNA) in formalin-fixed, paraffin-embedded tissue sections, using the commercially available anti-PCNA monoclonal antibody PC10. Normal epidermis served as a positive control and reference. In VC and warts, the PCNA-positive cells were principally located at the periphery of lesions, in the basal layer of the tumour islands. In some warts, however, stronger PCNA expressed was noted in the superficial layers, of the lesions corresponding to virus-infected keratinocytes (koilocytotic cells). In contrast, in SCC, PCNA-positive cells were randomly scattered throughout the tumours. Our findings suggest that, on the basis of mapping of PCNA distribution, VC resembles large warts or condylomata rather than typical SCC. Thus, VC appears to be a distinct clinical entity, intermediate between these two types of lesions, not only because of its clinical entity, intermediate between these two types of lesions, not only because of its clinical and virological features, but also with regard to its proliferative organization.

Carcinoma, Squamous Cell↗

Osteoarticular amyloidosis associated with haemodialysis: an immunoultrastructural study.

Osteoarticular amyloidosis occurred in a patient receiving long term haemodialysis. Histological examination showed that the amyloid deposit was surrounded by inflammatory cells and macrophages filled with haemosiderin. Electron microscopy showed that the amyloid fibrils were in close contact with cytoplasmic expansions, or located in intracytoplasmic pockets of the infiltrating cells. Immunohistological and immunoultrastructural observations confirmed that beta 2-microglobulin was a major constituent of amyloidosis associated with dialysis. Amyloid P component was also detected within the amyloid deposits. These findings suggest that amyloid P component, iron overload, or macrophage derived factors could have a role in the polymerisation of beta 2-microglobulin into amyloid deposit.

Amyloid↗