ObjectiveWe aimed to further improve knowledge about volar plate (VP) motion of the finger proximal interphalangeal joint (PIP), by analyzing the dynamic VP shape during a full range of finger flexion using magnetic resonance cinematography of the fingers (MRCF), and to compare the results with anatomical cross sections from cadaver specimens.Materials and methodsThe dynamic sagittal VP shape was visualized with MRCF in a total number of 23 healthy volunteers. The length, angle, and thickness as well as the contact length of the VP to the PIP joint base were measured. Statistical analysis included t-test or rank-sum testing. Anatomical cross sections with differing degrees of PIP joint flexion were obtained from 12 cadaver specimens (fingers) for comparison.ResultsSignificant positive correlations between PIP joint flexion angle and VP area, length, depth and the VP contact length were found. This matched histologically to fiber rearrangements especially within the loose third VP layer.ConclusionOur study analyzed the full range of motion dynamic VP shape of the PIP joint using MRCF. This contributes to a more precise understanding of the complex interaction of the VP with the PIP joint and may facilitate evaluation of clinical cases such as VP avulsion or pulley rupture.

Background/Aim: Transportation of ovarian cortex prior to freezing is used clinically; however, basic investigations of ovarian storage are limited and the question remains what temperature is optimal for transport over long distances and time periods. The aim of this study was to evaluate the rate of follicular loss over various time periods under two different temperatures and assess whether ovarian follicle viability is affected following cryopreservation and thawing subsequent to the transportation of ovarian tissue. Materials and Methods: Pig ovaries were transported at 4 degrees C (n=10) or at 38 degrees C (n=10) prior to cryopreservation. At 0, 4, 12 and 24 h tissues were fixed for histological examination and a LIVE/DEAD Assay. At the same time-points ovarian tissues were cryopreserved and analysed after thawing. Results: Histological evaluation and LIVE/DEAD Assay of freshly transported ovarian tissue showed significantly better follicle survival at 4 degrees C during transportation duration. In cryopreserved ovarian tissues the LIVE/DEAD Assay showed a significant difference in the number of intact and dead follicles at 24 h in favor of 4 degrees C (p<0.05). Conclusion: Ovarian tissue transportation should be kept at a minimum to prevent potential damage.

Background: Craniofacial osteosarcomas (COS) and extracranial osteosarcomas (EOS) show distinct clinical differences. COS show a remarkably lower incidence of metastases and a better survival. However, in contrast to EOS, they show a poor response to neoadjuvant chemotherapy. Tumor-associated macrophages and their polarization as well as developmental biological signaling pathways are possible candidates for explaining the clinical differences between COS and EOS. The aim of the study was to analyze differential expression of macrophage markers and important regulators of these pathways. Methods: Twenty osteosarcoma cases (10 COS and 10 EOS) were immunohistochemically stained to assess CD68, CD11c, CD163, MRC1, Gli1, and Gli2 expression. Statistical differences between COS and EOS were tested using the Mann-Whitney U test. Additionally, the paper describes an example of multidisciplinary treatment of a patient suffering from COS and discusses the surgical challenges in treatment and rehabilitation of COS. Results: COS showed a significantly (p < 0.05) increased infiltration of CD11c-positive M1 macrophages and a shift toward M1 polarization compared to EOS. Additionally, COS revealed a significantly (p < 0.05) lower Gli1 expression than EOS. Conclusion: The reduced Gli1 expression in COS can be interpreted as reduced activation of the Hedgehog (Hh) signaling pathway. The increased M1 polarization and reduced Hh activation in COS could explain the low incidence of metastases in these osteosarcomas.

Introduction . Asymmetric omphalopagus is a rare situation of conjoined twinning, in which a grossly defective twin is attached to the thorax and upper abdomen of the main twin. We describe a case of an asymmetric omphalopagus accompanied by a normal triplet after assisted reproductive technology (ART) and tried to further characterize the all aspects of the conjoined twins. Case Presentation : Perioperative diagnostic imaging was carried out followed by an autopsy to evaluate all aspects of the parasite accompanied by histological, immunohistochemical, and molecular biological evaluation. The parasite had well-developed lower extremities as well as upper extremities with a cleft hand syndrome. The sex was nondeterminable, but DNA fingerprinting revealed that both parasite and autosite are monozygotic, so are females. There was no sign of any axial skeleton or central nervous system. We found a rudimentary rectum with a nonpervious anus, a kidney, ureter, urinary bladder, and a blind-ending urethra. The blood supply of the parasite was connected to the vessel system of the autosite. Conclusions . To our knowledge, only two cases of parasitic omphalopagus after ART have been described to date. Altogether, 52 cases have been reported, and in most of them, the parasites were successfully separated.

In a previous radiostereometric analysis (RSA) of the Lubinus SP II (Link, Hamburg, Germany), which is one of the most often used cemented hip stems worldwide, our research group detected a very small but statistically significant distal migration of -0.03±0.17 mm 2 years after surgery compared to the postoperative radiograph. Maximum subsidence occurred between 6 and 12 months. The implant appeared to have stabilized after 2 years. The mean value of maximum total point motion (MTPM) was 0.99±0.69 mm, which was detected 2 years after surgery. The purpose of this study was to analyze the migration pattern and to verify the predictive value of short-term RSA of the Lubinus SP II stem after 10 years. After a follow-up of 5 and 10 years, 38 and 27 out of 100 patients remained available for further assessment, respectively. No statistically significant implant translation or rotation was found along or about the axes of the global coordinate system 5 and 10 years after surgery with respect to the postoperative radiograph. Furthermore, the MTPM was stable in both follow-up periods. The results suggest that the Lubinus SP II hip stem is still stable 10 years after surgery, supporting that determining prognosis by short-term RSA follow-up of 2 years could be an appropriate tool for appraisal of implant behavior 10 years after surgery.

BackgroundA male dizygotic twin was delivered at a gestational age of 36 weeks in the Children's Hospital of the Helios Medical Centre Wuppertal, Witten/Herdecke University Hospital.Contrary to his brother the boy presented dystrophic at birth (1.715 g birth weight; 150 g below 3rd percentile) and developed adverse gastrointestinal conditions within the first 2 months of life.These included chronic mucosal inflammation and oedematous lamina propria in the intestine, which contributed to intractable diarrhoea.At an age of 7 months the infant eventually died of enteral haemorrhages and liver failure.Further anamnesis revealed several similar fatalities in the familial clan with reportedly frequent parental consanguinity.Intractable chronic diarrhoea in infancy are heterogeneous disorders challenging for diagnostics and therapy.Despite extensive diagnostic approaches the etiology of many cases remains elusive.Investigating putatively underlying genetic disorders might clarify many cases. ResultsTo contribute to the diagnosis we performed whole exome sequencing of the affected infant as well as his twin brother and parents.We identified a suspicious nonsynonymous single nucleotide polymorphism (SNP) in the integrin beta-6 gene (ITGB6G1312A) entailing a V438M substitution.This SNP is very rare in the G1000 cohort and predicted being potentially harmful.The allelic distribution in the genotyped family members fit well with an autosomal recessive inheritance scheme.We performed computational biological and molecular biological analyses on the α V β6 integrin receptor function suggesting that the integrin α V β6 dimerization could be impaired, potentially causing a loss of α V β6 function in wound healing and epithelial tissue integrity. ConclusionsOur study provides a starting point for elucidating integrin α V β6 function and for understanding a pathomechanistical relevance of ITGB6V438M.

Introduction Modern anti-cancer strategies have distinctly increased survival rates; nevertheless, often accompanied by sterility. Currently, the only option for preserving fertility in prepubertal females is to cryopreserve ovarian tissue and retransplant frozen-thawed tissue to restore fertility after treatment. Our aim was to report the occurrence of repetitive antral follicle formation and oocyte maturation in a prepubescent ovarian tissue xenograft without exogenous hormone stimulation. Material and Methods Frozen-thawed ovarian tissue from a 6-year-old patient suffering from nephroblastoma was xenotransplanted in oophorectomized severe combined immunodeficiency (SCID) mice to evaluate follicle development. Ergebnisse Repetitive follicle development to the antral stage occurred in the same xenograft of prepubertal ovarian tissue without exogenous hormone administration; 37 days after retrieving a maturing oocyte (this first retrieval has been previously published), another, completely mature oocyte was harvested from the xenograft. Subsequent histological evaluation of the grafted tissue showed primordial follicles, nearly all stages of developing follicles, as well as large atretic ones. Many clusters with dormant primordial follicles were also present. Conclusion Xenotransplanted prepubertal ovarian tissue has the potential for repetitive oocyte retrieval cycles without administering exogenous hormones. The results indicate that the human ovarian tissue might be able to synchronize the hypothalamus-hypophysis-axes of the mouse to the physiological human cycle; this should be investigated in future studies.

In mice, conventional and plasmacytoid dendritic cells (DCs) derive from separate hematopoietic precursors before they migrate to peripheral tissues. Moreover, two classes of conventional DCs (cDC1 and cDC2 DCs) and one class of plasmacytoid DCs (pDCs) have been shown to be transcriptionally and functionally distinct entities. In humans, these three DC subtypes can be identified using the cell surface markers CD1c (cDC2), CD141 (cDC1), and CD303 (pDCs), albeit it remains elusive whether DC functionality is mainly determined by ontogeny or the tissue microenvironment. By phenotypic and transcriptional profiling of these three DC subtypes in different human tissues derived from a large number of human individuals, we demonstrate that DC subpopulations in organs of the lymphohematopoietic system (spleen, thymus, and blood) are strongly defined by ontogeny rather than by signals from the microenvironment. In contrast, DC subsets derived from human lung or skin differed substantially, strongly arguing that DCs react toward modulatory signals from tissue microenvironments. Collectively, the data obtained in this study may serve as a major resource to guide further studies into human DC biology during homeostasis and inflammation.

Severe generalized junctional epidermolysis bullosa, a lethal hereditary blistering disorder, is usually treated by palliative care. Allogeneic stem cell transplantation (SCT) has been proposed as a therapeutic approach, yet without clinical evidence. Decision making was evaluated retrospectively in 76 patients with severe generalized junctional epidermolysis bullosa born in the years 2000-2015. The diagnosis was based on the absence of laminin-332 in skin biopsies. With an incidence of 1 of 150,000, severe generalized junctional epidermolysis bullosa occurred more often than published previously. Eleven as yet unreported mutations in the laminin-332 genes were detected. Although patients homozygous for the LAMB3 mutation c. 1903C>T lived longer than the others, life expectancy was greatly diminished (10.8 vs. 4.6 months). Most patients failed to thrive. In two patients with initially normal weight gain, the decision for SCT from haploidentical bone marrow or peripheral blood was made. Despite transiently increasing skin erosions, the clinical status of both subjects stabilized for several weeks after SCT, but finally deteriorated. Graft cells, but no laminin-332, were detected in skin biopsies. The patients died 96 and 129 days after SCT, respectively, one of them after receiving additional skin grafts. Treatment of severe generalized junctional epidermolysis bullosa by SCT is a last-ditch attempt still lacking proof of efficacy.

Radiostereometric analysis (RSA) is the gold standard evaluating micromovements after total hip arthroplasty. The aim of this study was to investigate the migratory pattern of an uncemented femoral stem during the first 2 years after surgery. We followed 28 patients with a mean age of 57 (SD 13) years for the first two postoperative years. Radiostereometric analysis was used to measure the translation and rotation of the femoral component. The Harris hip score (HHS) was determined to evaluate the clinical outcome. No stem had to be revised. The mean HHS advanced from 35 (SD 11) preoperative to 89 (SD 10) 1 year after surgery. At the end of the observation period, mean subsidence of the stem was 0.26 mm (SD 0.82). Maximum total point motion (MTPM) was 1.23 mm (SD 1.22). The main distal migration took place up to 6 weeks after surgery with nearly no further subsidence up to 2 years postoperatively. All the measured migrations of the hip stem were very small. Results of the HHS demonstrate good clinical outcome. Long-term RSA is necessary to assess possible late migration of the Cerafit standard femoral stem.

Zusammenfassung Die Arthrose ist eine komplexe Erkrankung, die sowohl den Gelenkknorpel, aber auch den angrenzenden subchondralen Knochen und das Synovialgewebe beeinträchtigt, ihre Ätiologie ist multifaktoriell. Anders als bei den sekundären Formen der Arthrose, bei denen die Gelenkschädigung die Folge einer Erkrankung oder einer Überlastung ist, liegen die Ursachen der primären Formen im Knorpel selbst. Bei den primären Formen der Arthrose bestehen komplexe Interaktionen, bei denen sowohl multiple Zytokine als auch die von ihnen ausgelösten Veränderungen in der Homöostase des Knorpels zu einer langsamen Degeneration und schließlich Destruktion des Knorpels führen. Die Schädigung der Knorpelmatrix entwickelt sich durch die von den Zytokinen ausgelöste Überaktivität der eigentlich für Umbauvorgänge vorgesehenen Matrixmetalloproteasen. Einer der möglichen Auslöser für diese Veränderungen können „degenerative DNA-Veränderungen“ sein, die zu fokalen Schädigungen der DNA und durch die daraus folgende eingeschränkte Funktionsfähigkeit zu einem seneszenzartigen Verhalten der Chondrozyten führen.

Die pigmentierte villonoduläre Synovialitis (PVNS) ist eine seltene proliferative Erkrankung der Binnenhaut großer und kleiner Gelenke. Um ein optimales Behandlungsergebnis zu erzielen, sind eine spezifische Diagnostik und ein gezieltes therapeutisches Vorgehen notwendig.

We present an unusual case of a long-distance runner suffering from acute dissection of a common iliac artery (CIA) aneurysm with endofibrotic lesions. He suffered from acute pelvic and abdominal pain after exercise. Computed tomography angiography confirmed the dissecting aneurysm of the left CIA without signs of rupture. After cutdown, resection of the CIA and iliac bifurcation as well as bypass grafting was performed. Histologic examination confirmed endofibrotic lesions without calcifications. Complicated iliac artery aneurysm could be the result of endofibrotic lesions. Clinicians should keep this in mind, even if physical examination findings and the ankle-brachial index are normal at rest and after exercise.

A 17-year-old soccer player noticed intermittent claudication after reconvalescence from a severe blunt knee trauma with laceration of the anterior cruciate ligament. Physical examination revealed a pulseless right leg without rest pain. Magnetic resonance imaging documented a short occlusion of the popliteal artery with sparse but visible collaterals (A). Cross-sectional imaging demonstrated an atypical bundle or accessory insertion of the gastrocnemius muscle (popliteal entrapment syndrome type III) (B). Surgical exposure of the popliteal artery by a posterior approach showed a circumscript thickening of the vessel wall at a total length of 6 cm with occlusion of the lumen. Thus, resection of the causative anomalous muscle or fibrous tissue was combined with an interposition of a short vein graft. Macroscopic longitudinal section of the resected popliteal segment demonstrated thickening of the vessel wall by myointimal hyperplasia (C). Surprisingly, histological examination of the specimen demonstrated not only the expected myointimal hyperplasia but also segmental areas with calcification, which are uncommon in adolescents (D). After severe blunt knee trauma, an intimal tear is a typical complication.1Merrill K.D. Knee dislocations with vascular injuries.Orthop Clin North Am. 1994; 25: 707-713PubMed Google Scholar Because of more aggressive behavior, male children and young adults have the highest rates of vascular injury. This might be the reason to suspect initially a traumatic occlusion of the popliteal artery in this case. This case is special in all respects. Acute ischemia was not seen as a result of preexisting collaterals, and claudication was a delayed symptom only because of immobilization of the limb during reconvalescence and a progressive disease with collaterals. Histological examination documented severe myointimal hyperplasia of the popliteal artery and intramural ossifications. Studies on popliteal artery entrapment syndrome describe a median 24% prevalence of popliteal artery occlusion and a median 13.5% prevalence of poststenotic dilatation or aneurysm formation in the popliteal artery.2Sinha S. Houghton J. Holt P.J. Thompson M.M. Loftus I.M. Hinchliffe R.J. Popliteal entrapment syndrome.J Vasc Surg. 2012; 55: 252-262Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar Until now, this is the first case to verify a segmental wall calcification as a result of a repetitive popliteal trauma in adolescents.

Tenosynovial giant cell tumour (TSGCT; synonym, pigmented villonodular synovitis (PVNS)) is a rare low-grade mesenchymal neoplasm of either intra-articular or extra-articular origin. The etiopathogenesis of TSGCT is still uncertain, but recent studies showed a translocation involving colony-stimulating factor 1 (CSF-1) gene in a subset of cases. Histological features mimicking TSGCT can sometimes be encountered in periprosthetic interface membranes. To investigate the frequency and morphologic spectrum of this phenomenon, we conducted a systematic analysis of 477 periprosthetic interface membranes and performed immunohistochemical analysis on a subset of lesions compared to genuine TSGCT. In 26 of 477 periprosthetic membrane samples (5 %), at least some TSGCT-like features were found and 18 cases (4 %) strongly resembled it. Wear particles were detected in 100 % of the TSGCT-like lesions but only in 63.3 % of the whole cohort of periprosthetic membranes (p value <0.001). Immunohistochemistry comparing true TSGCT and TSGCT-like membranes showed similar inflammatory infiltrates with slightly elevated CD3+/CD8+ T lymphocytes and a slightly higher proliferation index in TSGCT samples. In conclusion, TSGCT-like changes in periprosthetic membranes likely represent exuberant fibrohistiocytic inflammatory response induced by wear particles and should be distinguished from genuine (neoplastic) TSGCT. Although TSGCT and TSGCT-like periprosthetic membranes represent different entities, their comparable morphology might reflect analogous morphogenesis.

Defining new therapeutic strategies to overcome therapy resistance due to tumor heterogeneity in colon cancer is challenging. One option is to explore the molecular profile of aggressive disseminating tumor cells. The cytoskeleton-associated Death-associated protein kinase ( DAPK) is involved in the cross talk between tumor and immune cells at the invasion front of colorectal cancer. Here dedifferentiated tumor cells histologically defined as tumor budding are associated with a high risk of metastasis and poor prognosis. Analyzing samples from 144 colorectal cancer patients we investigated immunhistochemical DAPK expression in different tumor regions such as center, invasion front, and buds. Functional consequences for tumor aggressiveness were studied in a panel of colon tumor cell lines using different migration, wound healing, and invasion assays. DAPK levels were experimentally modified by siRNA transfection and overexpression as well as inhibitor treatments. We found that DAPK expression was reduced towards the invasion front and was nearly absent in tumor buds. Applying the ECIS system with HCT116 and HCT116 stable lentiviral DAPK knock down cells (HCTshDAPK) we identified an important role for DAPK in decreasing the migratory capacity whereas proliferation was not affected. Furthermore, the migration pattern differed with HCTshDAPK cells showing a cluster-like migration of tumor cell groups. DAPK inhibitor treatment revealed that the migration rate was independent of DAPK's catalytic activity. Modulation of DAPK expression level in SW480 and DLD1 colorectal cancer cells significantly influenced wound closure rate. DAPK seems to be a major player that influences the migratory capability of disseminating tumor cells and possibly affects the dynamic interface between pro- and anti-survival factors at the invasion front of colorectal cancer. This interesting and new finding requires further evaluation.

Hypohidrotic ectodermal dysplasia (HED) is a rare disorder characterized by deficient development of structures derived from the ectoderm including hair, nails, eccrine glands, and teeth. HED forms that are caused by mutations in the genes EDA, EDAR, or EDARADD may show almost identical phenotypes, explained by a common signaling pathway. Proper interaction of the proteins encoded by these three genes is important for the activation of the NF-κB signaling pathway and subsequent transcription of the target genes. Mutations in the gene EDARADD are most rarely implicated in HED. Here we describe a novel missense mutation, c.367G>A (p.Asp123Asn), in this gene which did not appear to influence the interaction between EDAR and EDARADD proteins, but led to an impaired ability to activate NF-κB signaling. Female members of the affected family showed either unilateral or bilateral amazia. In addition, an affected girl developed bilateral ovarian teratomas, possibly associated with her genetic condition.

The ability to escape apoptosis is a hallmark of cancer-initiating cells and a key factor of resistance to oncolytic therapy. Here, we identify FAM96A as a ubiquitous, evolutionarily conserved apoptosome-activating protein and investigate its potential pro-apoptotic tumor suppressor function in gastrointestinal stromal tumors (GISTs). Interaction between FAM96A and apoptotic peptidase activating factor 1 (APAF1) was identified in yeast two-hybrid screen and further studied by deletion mutants, glutathione-S-transferase pull-down, co-immunoprecipitation and immunofluorescence. Effects of FAM96A overexpression and knock-down on apoptosis sensitivity were examined in cancer cells and zebrafish embryos. Expression of FAM96A in GISTs and histogenetically related cells including interstitial cells of Cajal (ICCs), "fibroblast-like cells" (FLCs) and ICC stem cells (ICC-SCs) was investigated by Northern blotting, reverse transcription—polymerase chain reaction, immunohistochemistry and Western immunoblotting. Tumorigenicity of GIST cells and transformed murine ICC-SCs stably transduced to re-express FAM96A was studied by xeno- and allografting into immunocompromised mice. FAM96A was found to bind APAF1 and to enhance the induction of mitochondrial apoptosis. FAM96A protein or mRNA was dramatically reduced or lost in 106 of 108 GIST samples representing three independent patient cohorts. Whereas ICCs, ICC-SCs and FLCs, the presumed normal counterparts of GIST, were found to robustly express FAM96A protein and mRNA, FAM96A expression was much reduced in tumorigenic ICC-SCs. Re-expression of FAM96A in GIST cells and transformed ICC-SCs increased apoptosis sensitivity and diminished tumorigenicity. Our data suggest FAM96A is a novel pro-apoptotic tumor suppressor that is lost during GIST tumorigenesis.

Confocal laser scanning microscopy is an advanced technique for imaging tissue samples in vitro and in vivo at high optical resolution. The development of new fluorochrome variants do not only make it possible to perform multicolor flow cytometry of single cells, but in combination with high resolution laser scanning systems also to investigate the distribution of cells in lymphoid tissues by confocal immunofluorescence analyses, thus allowing the distinction of various cell populations directly in the tissue. Here, we provide a protocol for the visualization of at least six differently fluorochrome-labeled antibodies at the same time using a conventional confocal laser scanning microscope with four laser lines (405 nm, 488 nm, 555 nm, and 639 nm laser wavelength) in both murine and human tissue samples. We further demonstrate that compensation correction algorithms are not necessary to reduce spillover of fluorochromes into other channels when the used fluorochromes are combined according to their specific emission bands and the varying Stokes shift for co-excited fluorochromes with the same laser line.