Decreased expression of GPC1 in human skin keratinocytes and epidermis during ageing.

BACKGROUND: Glypicans (GPCs) are heparan sulfate cell membrane proteoglycans containing glycosylphosphatidylinositol (GPI) anchor. They play important role in cell behavior by activating/presenting numerous growth factors and cytokines. OBJECTIVES: The expression of GPCs was investigated in primary culture of skin keratinocytes sampled from healthy donors of different age. MATERIALS AND METHODS: Primary keratinocytes from healthy female donors aged from 20 to 89 years old (n = 30) were either isolated from breast or abdominal skin samples (n = 27) or purchased (n = 3). GPCs expression was examined by qPCR, immunohistochemistry and western blot. Its role in proliferation induced by fibroblast growth factor 2 (FGF2) was also studied. RESULTS: Glypican 1 (GPC1) was the major expressed GPC in human keratinocytes. Its expression was up to two orders of magnitude higher than other GPCs and was significantly decreased with the age of the donors. It was localized at the cell surface and associated with intracellular granules. In skin sections, GPC1 was mainly localized in basal layer of epidermis. Shedding of GPCs decreased the proliferative effect of FGF2, confirming their role of modulator of growth factor effects on keratinocytes. These results established GPC1 as an important player in epidermis biology and skin ageing.

Adjuvant radiation therapy for malignant Abrikossoff's tumor: a case report about a femoral triangle localisation.

BACKGROUND: Granular cell or Abrikossoff's tumors are usually benign however rare malignant forms concern 1 to 3% of cases reported. Pelvic locations are exceptional. CASE PRESENTATION: We report a case of a 43-years-old patient who had a benign Abrikossoff's tumor localized in the right femoral triangle diagnosed at the biopsy. The patient underwent a surgical tumorectomy and inguinal lymph nodes resection. Histologically, the tumor showed enough criteria to give diagnosis of malignancy: nuclear pleomorphism, tumor cell spindling, vesicular nuclei with large nucleoli. Moreover, five lymph nodes were metastatic. Immunohistochemistry findings confirmed the diagnosis of granular cell tumor which is positive for S100 protein and CD68 antibodies. The mitotic index was nevertheless low with a Ki67 labeling index of 1-2%. A large surgical revision with an inguinal curage following radiotherapy were decided on oncology committee. Adjuvant radiotherapy on the tumor bed and right inguinal area of ​​50 Gy in conventional fractionation was delivered with the aim of reducing local recurrence risk. There was no recurrence on longer follow-up (10 months post radiotherapy). CONCLUSIONS: Adjuvant radiotherapy seems an appropriate therapeutic approach, even if controversial, given that some authors report effectiveness on local disease progression.

Identification of CD245 as myosin 18A, a receptor for surfactant A: A novel pathway for activating human NK lymphocytes.

CD245 is a human surface antigen expressed on peripheral blood lymphocytes, initially delineated by two monoclonal antibodies DY12 and DY35. Until now, CD245 molecular and functional characteristics remained largely unknown. We combined immunological and proteomic approaches and identified CD245 as the unconventional myosin 18A, a highly conserved motor enzyme reported as a receptor for the surfactant protein A (SP-A), that plays a critical role in cytoskeleton organization and Golgi budding. We report that the recruitment of CD245 strongly enhanced NK cell cytotoxicity. Further, we show that the enhancement of the NK lymphocytes killing ability toward CD137-ligand expressing target cells could result from the induction of CD137 expression following CD245 engagement. The SP-A receptor could therefore represent a novel and promising target in cancer immunotherapy.

Belgian consensus guidelines for follow-up of women with cervical cytological abnormalities.

In medical care cervical cancer screening is important because it enables the detection of precancer and cancer at an early stage. By adequate treatment after a screening-detected lesion it helps to reduce the mortality related to cervical cancer. Worldwide, many millions of women have smears taken at a more or less regular base and of these, approximately 7% are abnormal, and follow-up is thus required.As this represents an important cost in medical health care and has serious consequences for the affected women, it is important to have uniform and clear guidelines to allow an optimal follow-up and clinical management. A system for the uniform reporting of cervical cytology has been designed by the National Cancer Institute (U.S.A.) and resulted in the Bethesda System 1991. The present paper and the terminology used are based on the Bethesda System revised in 2001. It explains the guidelines, based on the 2001 Bethesda System and the 2004 consensus guidelines for the management of women with cervical cytological abnormalities, as developed by the members of the Board of the Belgian Society of Clinical Cytology, and adapted to the Belgian situation.

Is urinary tract cytology still useful for diagnosis of bladder carcinomas? A large series of 592 bladder washings using a five-category classification of different cytological diagnoses.

BACKGROUND: The aim of this study was to estimate the efficiency of a recent five-category urinary cytological classification. METHODS: A total of 592 bladder washings were fixed immediately with Saccomanno's fixative. All samples were centrifuged in a Hettich cyto-centrifuge. For each sample, the reference standard was the histology when a lesion was present at the time of cystoscopy. A five-category cytological classification was used: negative, suspicious of low (S-Lg) or high (S-Hg) grade neoplasia and consistent with low (Lg) or high (Hg) grade neoplasia. RESULTS: For cytological diagnoses of S-Lg and Lg, sensitivity was 37% and specificity was 95% for the histological diagnosis of low-grade non-invasive urothelial papillary tumour (Lg-UPT), which included papillary urothelial neoplasm of low malignant potential and low-grade urothelial carcinoma. For cytological diagnosis of S-Hg and Hg, sensitivity was 44% for high-grade non-invasive urothelial papillary carcinoma (Hg-UPC), 70% for carcinoma in situ (CIS) and 81% for invasive carcinoma (T1 and higher). Specificity was 99% in each case. Cytological diagnosis of S-Hg or Hg was not found for Lg-UPT (0/59) and no cytological diagnosis of S-Lg or Lg was found for invasive carcinoma, but was seen for Hg-UPC in 10% (3/28) and for CIS in 6% (3/50) of cases. CONCLUSION: Despite the absence of international consensus, the recent five-category cytological classification for urine is accurate for current urological practice.

MR imaging, proton MR spectroscopy, ultrasonographic, histologic findings in patients with chronic lymphedema.

Lymphedema is a progressive disease with multiple alterations occurring in the dermis. We undertook this study using high-frequency ultrasonography (US), magnetic resonance imaging, proton MR spectroscopy and histology to examine structural changes occurring in the subcutaneous tissue and precisely describe the nature of intralobular changes in chronic lymphedema. Four cutaneous and subcutaneous tissue biopsies from patients with chronic lymphedema during lymphonodal transplantation were studied. We performed US with a 13.5 MHz transducer, TSE T1 and TSE T2 magnetic resonance images with and without fat-suppression, MR Chemical Shift Imaging Spectroscopy and histological evaluation on these biopsies. We found that normal subcutaneous septa are seen as hyperechogenic lines in US and hyposignal lines in MRI and that hyperechogenic subcutis in US can be due to interlobular and intralobular water accumulation and/or to interlobular and intralobular fibrosis. Our study also confirms the usefulness of MR spectroscopy to assess water or fat content of soft tissue. Thus, multiple imaging modalities may be necessary to precisely delineate the nature of tissue alterations in chronic lymphedema.

Antigens and granularity of blood monocytes in relation to inflammatory markers and lipids in postmenopausal women.

OBJECTIVES: The menopause is associated with an increase of inflammatory markers (C-reactive protein, fibrinogen), cytokines (INFgamma, TNF, etc.) and blood lipoproteins. In vitro, CRP, LDL and fibrinogen can modulate or potentiate interleukines production by monocytes. The aim of this work was to study, the relationships in vivo between hs-CRP, fibrinogen, lipoproteins and the phenotype of circulating monocytes. METHODS: The monocytes phenotype, in postmenopausal women (n=26) without history of cardiovascular disease, was determined, by flow cytometry, measuring granularity and CD14, HLA-DR and CD62-L antigens expression. Blood monocytes were divided in CD14+dim monocytes (low CD14 expression) and CD14+bright monocytes (high CD14 expression). RESULTS: HLA-DR was negatively correlated with hs-CRP and fibrinogen. The relationships between ApoB, LDL/ApoB ratio and CD14 expression was restricted to the CD14+bright monocytes. Blood lipids, i.e. total cholesterol, LDL-c and ApoB were correlated with the granularity of both subsets. CD14+dim monocytes were characterized by a low granularity and CD62-L expression. CONCLUSIONS: Our data show that fibrinogen and hs-CRP are correlated with a reduced antigen-presenting capacity. Expression of CD14 on CD14+bright monocytes is negatively associated to atherogenic LDL. Blood monocytes granularity was positively correlated with serum lipids indicating that monocytes could uptake modified LDL in circulation and not restricted to subendothelial space.

Pathological aspects of beta(2)-microglobulin amyloidosis.

Histology remains the gold standard to diagnose beta(2)-microglobulin amyloidosis (A beta(2)M). Two diagnostic criteria are required: positive Congo red staining with typical birefringence under polarized light and immunostaining of amyloid deposits with a labeled anti-beta(2)M antibody. A beta(2)M is preferentially located in the joints. Small deposits are also found in various organs, mainly the heart and gastrointestinal tract. Pathologic studies have demonstrated a high prevalence of articular A beta(2)M early in the course of hemodialysis and peritoneal dialysis, antedating clinical manifestations by several years. The stages of beta(2)M amyloid formation have been delineated: beta(2)M amyloid deposits first on the surface of the cartilage, in the absence of macrophages (stage 1), and subsequently involves capsules and synovia (stage 2), with eventual recruitment of macrophages around large beta(2)M amyloid deposits (stage 3). Clinical manifestations are likely associated with the inflammation observed in stage 3. The factors triggering the fibrillar precipitation of beta(2)M remain unknown. Macrophages do not play a role: their presence is the consequence rather than the cause of beta(2)M amyloid deposits. Several substances coprecipitated with beta(2)M amyloid have been incriminated: highly sulfated glycosaminoglycans such as chondroitin or keratan sulfate, antiproteases such as alpha(2)-macroglobulin, and apolipoprotein E. As yet, no definitive conclusion has been reached.

Cardiac troponins I and T are biological markers of left ventricular dysfunction in septic shock.

BACKGROUND: Cardiac depression in severe sepsis and septic shock is characterized by left ventricular (LV) failure. To date, it is unclear whether clinically unrecognized myocardial cell injury accompanies, causes, or results from this decreased cardiac performance. We therefore studied the relationship between cardiac troponin I (cTnI) and T (cTnT) and LV dysfunction in early septic shock. METHODS: Forty-six patients were consecutively enrolled, fluid-resuscitated, and treated with catecholamines. Cardiac markers were measured at study entry and after 24 and 48 h. LV function was assessed by two-dimensional transesophageal echocardiography. RESULTS: Increased plasma concentrations of cTnI (>/=0.4 microgram/L) and cTnT (>/=0.1 microgram/L) were found in 50% and 36%, respectively, of the patients at one or more time points. cTnI and cTnT were significantly correlated (r = 0.847; P <0.0001). Compared with cTnI-negative patients, cTnI-positive subjects were older, presented higher Acute Physiology and Chronic Health Evaluation II scores at diagnosis, and tended to have a worse survival rate and a more frequent history of arterial hypertension or previous myocardial infarction. In contrast, the two groups did not differ in type of infection or pathogen, or in dose and type of catecholamine administered. Continuous electrocardiographic monitoring in all patients and autopsy in 12 nonsurvivors did not disclose the occurrence of acute ischemia during the first 48 h of observation. LV dysfunction was strongly associated with cTnI positivity (78% vs 9% in cTnI-negative patients; P <0.001). In multiple regression analysis, both cTnI and cTnT were exclusively associated with LV dysfunction (P <0.0001). CONCLUSIONS: These findings suggest that in septic shock, clinically unrecognized myocardial cell injury is a marker of LV dysfunction. The latter condition tends to occur more often in severely ill older patients with underlying cardiovascular disease. Further studies are needed to determine the extent to which myocardial damage is a cause or a consequence of LV dysfunction.

Histological characteristics of sternoclavicular beta 2-microglobulin amyloidosis and clues for its histogenesis.

BACKGROUND: The pathogenesis of beta 2-microglobulin amyloidosis (A beta 2m) has yet to be fully elucidated. METHODS: We describe the distribution and extent of A beta 2m deposition and macrophagic infiltration in cartilage, capsule, and synovium of sternoclavicular joints obtained postmortem from 54 patients after 3 to 244 (median 46) months of dialysis. Twenty-four nonuremic patients served as a control group. The diagnosis of amyloidosis (A) rested on a positive Congo Red staining (typical birefringence) and that of A beta 2m on positive immunostaining of the A deposits with a monoclonal anti-beta 2m antibody. The size of A deposits was measured. RESULTS: A beta 2m was detected in 32 (59%), and non-beta 2m amyloid (Anon beta 2m) was detected in an additional 8 (15%) of the 54 dialyzed patients. A beta 2m deposits were present in the cartilage of all A beta 2m (+) patients (100%). They were localized solely in the cartilage in 27% of the cases, either as a thin patchy layer or as a continuous thicker layer (identified as stage I). A beta 2m was additionally present in the capsule and/or synovium without macrophages in 27% of the cases (identified as stage II). The correlation between the size of cartilaginous deposits and dialysis duration (P = 0.02) as well as with the prevalence (P = 0.03) and size of capsular deposits (P = 0.02) suggests that stage II is a later stage of A deposition. Clusters of macrophages were detected around capsular and synovial amyloid deposits in 46% of the cases (identified as stage III). The longer duration of dialysis in those with stage III as well as the relationship between the size of the A beta 2m deposits and the prevalence of macrophagic infiltration suggests that stage III is the last stage of A beta 2m deposition. Marginal bone erosions were observed in 9 out of 12 patients with stage III deposits. Their size was correlated with that of cartilaginous deposits (P = 0.01). Among the 24 control patients, Anon beta 2m was detected in 12 patients (cartilage 100%, capsule 8%, synovium 30%). CONCLUSIONS: The earliest stage of A beta 2m deposition occurs in the cartilage. A beta 2m subsequently extends to capsule and synovium. These two first stages do not require macrophage infiltration. Macrophages are eventually recruited around larger synovial or capsular deposits in the final stage. Marginal bone erosions develop in this late stage.

[Maxillary actinomycosis and maxillary candidiasis in the immunocompetent patient]. / Actinomycose et candidose du sinus maxillaire chez le patient immunocompétent.

Two distinct cases of maxillary actinomycosis and maxillary candidosis in immunocompetent hosts are reported; These infections are rare and similar to mycotic extramucosal non allergic sinusitis. Microbiology and microscopic examination are mandatory to prompt and successful management. Endoscopic endonasal surgery by middle meatotomy seems to be an adequate treatment for these particular entities.

[Schwannoma of the cervical esophagus: case report and clinical and pathological analysis]. / Schwannome de l'oesophage cervical: présentation d'un cas avec analyse clinique et pathologique.

Neurogenic tumors fo the head and neck are relatively rare and often mistaken for other disease processes. Schwannoma (neurinoma, neurilemoma, neurolemoma) is a tumour histologically characterized by the proliferation of schwann cells from the neural sheath of autonomic, cranial or peripheral nerves. We describe a case of schwannoma located in the muscular layer of the cervical esophagus. The clinical and radiological findings are highlighted allowing a retrospective preoperative presumption of schwannoma. Esophageal schwannoma is a very rare entity as only nine cases have been reported so far.

Prevalence of histological beta2-microglobulin amyloidosis in CAPD patients compared with hemodialysis patients.

BACKGROUND: The prevalence of beta2-microglobulin amyloidosis (Abeta2m) in patients on continuous ambulatory peritoneal dialysis (CAPD) is unknown. METHODS: We prospectively obtained a median of 2 (range 1 to 4) joint samples from 26 CAPD patients aged 44 to 93 (median 73) years at post-mortem evaluation after 4.5 to 126 (median 27) months solely on CAPD (N = 19) or primarily on CAPD (that is, < or = 10% and < or = 1 year of renal replacement therapy time on other modalities; N = 7). The diagnosis of Abeta2m rested on Congo red staining (typical birefringence) and positive immunostaining of amyloid deposits by a monoclonal anti-beta2m antibody. RESULTS: Abeta2m was diagnosed in 8 of 26 patients (31%). Prevalence ranged from 20% (2 of 10 patients) within < or = 24 months CAPD to 30% (3 of 10 patients) after 24 to 48 months and 50% (3 of 6 patients) after 49 to 126 months (P = 0.11). The prevalence of Abeta2m was similar in patients without or with one or more peritonitis episodes. No significant difference in prevalence (P = 0.118) was found between CAPD patients (8+/26; 31%) and hemodialysis patients (13+/26; 50%) carefully matched for time on dialysis and age at the onset of dialysis. CONCLUSIONS: The prevalence of histological Abeta2m reaches 31% after a median duration of 27 months of CAPD. This prevalence is not significantly different from that observed in a group of HD patients matched for age and dialysis duration.

Treated plasma cell lesions of bone with MRI signs of response to treatment: unexpected pathological findings.

Two cases of treated plasma cell lesions of bone are reported for which contrast-enhanced MRI had suggested necrosis, based on lack of enhancement after gadolinium injection, and in which pathologic examinations revealed the presence of extensive viable neoplastic tissue. These cases highlight the need for cautious interpretation of contrast-enhanced MRI signs of response to treatment and inactivity of lesions in the setting of plasma cell neoplasms.

Histological prevalence of beta 2-microglobulin amyloidosis in hemodialysis: a prospective post-mortem study.

The histological prevalence of beta-2 microglobulin amyloidosis (A beta 2m) was evaluated in a prospective study of joint samples obtained at autopsy in 54 patients on hemodialysis (HD) for 2 to 163 (median 47) months, aged 20 to 80 (median 63) years at HD onset. Carpal tunnel syndrome surgery or radiological signs of A beta 2m were present in 2 and 4% of them, respectively. A control group of 34 patients without end-stage renal disease, autopsied during the same period was used as a reference. The 153 sampled joints (1 to 8, median 2 per patient) were sternoclavicular joints (N = 77), shoulders (N = 35), knees (N = 28), others (N = 13). A beta 2m was diagnosed (positive Congo red with typical birefringence and positive immunostaining of deposits for beta 2m) in 26 of 54 (48%) patients. Prevalence reached respectively 21%, 33%, 50%, 90% and 100% within two years, after 2 to 4 years, 4 to 7 years, 7 to 13 years and more than 13 years HD. The calculated sensitivity of the various joints for A beta 2m detection is significantly higher (P < 0.03) for sternoclavicular joints (97%) and knees (91%) than for shoulders (57%). Multivariate stepwise logistic regression with discriminant analysis identified both HD duration (P = 0.0008) and age at HD onset (P = 0.0093) but not diabetic nephropathy (P = 0.23) or gender (P = 0.25) as independent risk factors for A beta 2m. The probability of joint A beta 2m was quantitated as a function of age and HD duration. In conclusion, A beta 2m may be observed in the large joints early after HD onset. Overall prevalence reaches 48% of the patients on HD for a median of 47 months. It is much higher than that reported on the basis of clinical or radiological evidence. The sternoclavicular and knee joints are more frequently (P < 0.03) involved than the shoulder. The easily accessible sternoclavicular joint therefore appears to be the best site for the early detection of A beta 2m. Both HD duration and age at HD onset, but not diabetic nephropathy, are independent risk factors for A beta 2m.