Transmaternal cell flow leads to antigen-experienced cord blood

Umbilical cord blood (UCB) is used for HSCT. It is known that UCB can comprise Ag-specific T cells. Here we question whether solely transmaternal cell flow may immunize UCB. Twenty-three female UCB samples were collected from healthy mothers and analyzed for minor histocompatibility Ag HY-specific responses. Forty-two of 104 tetramer(pos) T-cell clones, isolated from 16 of 17 UCB samples, showed male-specific lysis in vitro. Male microchimerism was present in 6 of 12 UCB samples analyzed. In conclusion, female UCB comprises HY-specific cytotoxic T cells. The immunization is presumably caused by transmaternal cell flow of male microchimerism present in the mother. The presence of immune cells in UCB that are not directed against maternal foreign Ags is remarkable and may explain the reported clinical observation of improved HSCT outcome with younger sibling donors.     

WNT Signaling and Cartilage: Of Mice and Men

In adult articular cartilage, the extracellular matrix is maintained by a balance between the degradation and the synthesis of matrix components. Chondrocytes that sparsely reside in the matrix and rarely proliferate are the key cellular mediators for cartilage homeostasis. There are indications for the involvement of the WNT signaling pathway in maintaining articular cartilage. Various WNTs are involved in the subsequent stages of chondrocyte differentiation during development, and deregulation of WNT signaling was observed in cartilage degeneration. Even though gene expression and protein synthesis can be activated upon injury, articular cartilage has a limited ability of self-repair and efforts to regenerate articular cartilage have so far not been successful. Because WNT signaling was found to be involved in the development and maintenance of cartilage as well as in the degeneration of cartilage, interfering with this pathway might contribute to improving cartilage regeneration. However, most of the studies on elucidating the role of WNT signaling in these processes were conducted using in vitro or in vivo animal models. Discrepancies have been found in the role of WNT signaling between chondrocytes of mouse and human origin, and extrapolation of results from mouse models to the human situation remains a challenge. Elucidation of detailed WNT signaling functions will provide knowledge to improve cartilage regeneration.     

Undiagnosed and comorbid disorders in patients with presumed chronic fatigue syndrome

Objective

To assess undiagnosed and comorbid disorders in patients referred to a tertiary care center with a presumed diagnosis of chronic fatigue syndrome (CFS).

Methods

Patients referred for chronic unexplained fatigue entered an integrated diagnostic pathway, including internal medicine assessment, psychodiagnostic screening, physiotherapeutic assessment and polysomnography + multiple sleep latency testing. Final diagnosis resulted from a multidisciplinary team discussion. Fukuda criteria were used for the diagnosis of CFS, DSM-IV-TR criteria for psychiatric disorders, ICSD-2 criteria for sleep disorders.

Results

Out of 377 patients referred, 279 (74.0%) were included in the study [84.9% female; mean age 38.8 years (SD 10.3)].A diagnosis of unequivocal CFS was made in 23.3%. In 21.1%, CFS was associated with a sleep disorder and/or psychiatric disorder, not invalidating the diagnosis of CFS. A predominant sleep disorder was found in 9.7%, 19.0% had a psychiatric disorder and 20.8% a combination of both. Only 2.2% was diagnosed with a classical internal disease.In the total sample, a sleep disorder was found in 49.8%, especially obstructive sleep apnea syndrome, followed by psychophysiologic insomnia and periodic limb movement disorder. A psychiatric disorder was diagnosed in 45.2%; mostly mood and anxiety disorder.

Conclusions

A multidisciplinary approach to presumed CFS yields unequivocal CFS in only a minority of patients, and reveals a broad spectrum of exclusionary or comorbid conditions within the domains of sleep medicine and psychiatry. These findings favor a systematic diagnostic approach to CFS, suitable to identify a wide range of diagnostic categories that may be subject to dedicated care.     

A multidisciplinary approach to clitoral reconstruction after female genital mutilation: the crucial role of counselling

Objectives: Female genital mutilation (FGM) is becoming more widely seen in the West, due to immigration and population movement. Health services are being confronted with the need to provide care for women with FGM. One of the more recent trends is the provision of clitoral reconstruction. It remains unclear, however, what constitutes good practice with regard to this type of surgery. Methods: Based on a keynote presentation about reconstructive clitoral surgery, we briefly discuss the possible consequences of FGM and the findings from recent publications on clitoral reconstruction. Recognising individual differences in women, we suggest a multidisciplinary counselling model to provide appropriate care for women requesting clitoral reconstruction. Results: The literature shows that FGM influences physical, mental and sexual health. Clitoral reconstructive surgery can lead to an increase in sexual satisfaction and orgasm in some, but not all, women. A multidisciplinary approach would enable a more satisfactory and individually tailored approach to care. The multidisciplinary team should consist of a midwife, a gynaecological surgeon, a psychologist-psychotherapist, a sexologist and a social worker. Comprehensive health counselling should be the common thread in this model of care. Our proposed care pathway starts with taking a thorough history, followed by medical, psychological and sexological consultations. Conclusions: Women with FGM requesting clitoral reconstruction might primarily be looking to improve their sexual life, to recover their identity and to reduce pain. Surgery may not always be the right answer. Thorough counselling that includes medical, psychological and sexual advice is therefore necessary as part of a multidisciplinary approach.     

Antibody GD3G7 selected against embryonic glycosaminoglycans defines chondroitin sulfate-E domains highly up-regulated in ovarian cancer and involved in vascular endothelial growth factor binding

Chondroitin sulfate (CS) is abundantly present in the tumor stroma, and tumor-specific CS modifications might be potential targets to influence tumor development. We applied the phage display technology to select antibodies that identify these tumor-specific CS modifications. Antibody GD3G7 was selected against embryonic glycosaminoglycans, and it reacted strongly with CS-E (rich in GlcA-GalNAc4S6S units). In ovarian adenocarcinomas, strong expression of this CS-E epitope was found in the extracellular matrix, and occasionally on tumor cells. No expression was found in normal ovary and cystadenomas. Differential expression was found in ovarian carcinoma cell lines, which correlated with the gene expression of the GalNAc4S-6st enzyme, involved in biosynthesis of CS-E. Vascular endothelial growth factor (VEGF)-sensitive fenestrated (in normal tissues) and tumor blood vessels were both identified by antibody GD3G7, which might implicate a role for CS-E in VEGF biology. VEGF bound to CS-E and antibody GD3G7 could compete for binding of VEGF to CS-E. In conclusion, antibody GD3G7 identified rare CS-E-like structures that were strongly expressed in ovarian adenocarcinomas. This antibody might therefore be instrumental for identifying tumor-related CS alterations.