Genome Wide DNA Methylation Profiles Provide Clues to the Origin and Pathogenesis of Germ Cell Tumors

The cell of origin of the five subtypes (I-V) of germ cell tumors (GCTs) are assumed to be germ cells from different maturation stages. This is (potentially) reflected in their methylation status as fetal maturing primordial germ cells are globally demethylated during migration from the yolk sac to the gonad. Imprinted regions are erased in the gonad and later become uniparentally imprinted according to fetal sex. Here, 91 GCTs (type I-IV) and four cell lines were profiled (Illumina’s HumanMethylation450BeadChip). Data was pre-processed controlling for cross hybridization, SNPs, detection rate, probe-type bias and batch effects. The annotation was extended, covering snRNAs/microRNAs, repeat elements and imprinted regions. A Hidden Markov Model-based genome segmentation was devised to identify differentially methylated genomic regions. Methylation profiles allowed for separation of clusters of non-seminomas (type II), seminomas/dysgerminomas (type II), spermatocytic seminomas (type III) and teratomas/dermoid cysts (type I/IV). The seminomas, dysgerminomas and spermatocytic seminomas were globally hypomethylated, in line with previous reports and their demethylated precursor. Differential methylation and imprinting status between subtypes reflected their presumed cell of origin. Ovarian type I teratomas and dermoid cysts showed (partial) sex specific uniparental maternal imprinting. The spermatocytic seminomas showed uniparental paternal imprinting while testicular teratomas exhibited partial imprinting erasure. Somatic imprinting in type II GCTs might indicate a cell of origin after global demethylation but before imprinting erasure. This is earlier than previously described, but agrees with the totipotent/embryonic stem cell like potential of type II GCTs and their rare extra-gonadal localization. The results support the common origin of the type I teratomas and show strong similarity between ovarian type I teratomas and dermoid cysts. In conclusion, we identified specific and global methylation differences between GCT subtypes, providing insight into their developmental timing and underlying developmental biology. Data and extended annotation are deposited at GEO (GSE58538 and GPL18809).     

Volume maintenance of inlay bone grafts in the craniofacial skeleton

Although the clinical use of inlay bone grafts is widespread in craniofacial surgery, the dynamics of inlay bone grafting to the craniofacial skeleton have never been well characterized. Previous work demonstrated that volume maintenance of bone grafts in the onlay position is a consequence of their microarchitectural features, rather than their embryological origins. The purpose of this study was to investigate whether the properties determining the volume maintenance of bone grafts in the onlay position in the craniofacial skeleton could be extended to bone grafts in the inlay position. It was hypothesized that volume maintenance of an inlay bone graft could be better explained on the basis of the microarchitectural features of the graft (cortical versus cancellous composition), rather than its embryological origin (membranous versus endochondral), and that the primary determinant of bone graft behavior is the interaction between the microarchitectural features of the bone graft and the local mechanical environment in which the bone graft is placed. Cortical and cancellous bone grafts were harvested from the iliac crest (endochondral origin) of 25 New Zealand white rabbits, and cortical bone was harvested from the mandible (membranous origin) of each rabbit. Four 7-mm trephine holes were made in the cranium of each rabbit, posterior to the coronal suture. Each defect was filled with endochondral cortical bone, endochondral cancellous bone, or membranous cortical bone or was left as an ungrafted control specimen. Animals were killed at 3, 8, or 16 weeks. Crania were subjected to micro-computed tomographic and histological assessments. Micro-computed tomographic analysis demonstrated significant increases in actual bone volume from time 0 to the time of death for all types of grafts. Cortical bone demonstrated significant increases in space-occupying volume at all time points. By 16 weeks, no statistically significant difference in either the actual bone volume or the space-occupying volume according to graft type could be detected. There was no resorption of the inlay bone grafts; in fact, all bone types exhibited increased volume. Cancellous bone demonstrated the greatest capacity to increase actual bone volume. All bone graft types seemed to reach a steady-state bone volume, as if controlled by a local regulator. The regulator is likely the local mechanical environment in which the grafts were placed, as corroborated by the findings that the bone grafts seemed to recapitulate the characteristics of the bone in which they were placed, rather than maintaining their native characteristics.     

Heart and craniofacial muscle development: A new developmental theme of distinct myogenic fields

Head muscle development has been studied less intensively than myogenesis in the trunk, although this situation is gradually changing, as embryological and genetic insights accumulate. This review focuses on novel studies of the origins, composition and evolution of distinct craniofacial muscles. Cellular and molecular parallels are drawn between cardiac and branchiomeric muscle developmental programs, both of which utilize multiple lineages with distinct developmental histories, and argue for the tissues' common evolutionary origin. In addition, there is increasing evidence that the specification of skeletal muscles in the head appears to be distinct from that operating in the trunk: considerable variation among the different craniofacial muscle groups is seen, in a manner resembling myogenic specification in lower organisms.     

Periorbital lymphatic malformation: clinical course and management in 42 patients

Lymphatic malformation in the orbital cavity and surrounding region often causes disfigurement and visual problems. To better clarify the evolution and treatment of this condition, the authors studied a retrospective cohort of 42 consecutive patients seen between 1971 and 2003 and analyzed anatomic features, complications, and management. The ratio of female to male patients was 1:1. Most periorbital lymphatic malformations were noted at birth (59 percent), presenting as either unilateral swelling (60 percent) or a periorbital mass (24 percent). Sixty-two percent of lesions were on the left side. The ipsilateral cheek, temple, and forehead also were involved in 57 percent of patients. Twenty-two percent of lesions were intraconal, 30 percent were extraconal, and 48 percent were in both spaces. Forty-five percent of children had an associated cerebral developmental venous anomaly. Periorbital lymphatic malformation caused major morbidity; 52 percent of patients had intralesional bleeding and 26 percent of patients had a history of infection. Other common complications included intermittent swelling (76 percent), blepharoptosis (52 percent), proptosis (45 percent), pain (21 percent), amblyopia (33 percent), chemosis (19 percent), astigmatism (17 percent), and strabismus (7 percent). Ultimately, 40 percent of children had diminished vision and 7 percent became blind in the affected eye. Management of periorbital lymphatic malformation involved an interdisciplinary team that included an interventional radiologist, a craniofacial surgeon, and an ophthalmologist. The two therapeutic strategies were sclerotherapy (40 percent) and resection (57 percent); most patients required several interventions. A coronal approach was used for subtotal excision of fronto-temporal-orbital lymphatic malformation in 13 patients, whereas a tarsal incision was used for lesions isolated to the eyelid (n = 14). Ocular proptosis was temporarily managed by tarsorrhaphy (n = 9), but expansion of the bony orbit was needed to correct persistent proptosis (n = 8). Orbital exenteration was necessary in two patients.     

Craniofacial dermoids

Thirty-two patients with nasal dermal sinuses and cysts were treated during the 10-year period from 1978 to 1987. These patients presented with midline cysts (N = 18) or sinus ostia (N = 14). Only 6 of the 32 patients manifested intracranial extension (19 percent). All the patients with intracranial extension exhibited an intracranial mass on preoperative CT scans. Ten patients with no CT evidence of intracranial mass were noted to have only a fibrous cord extending to the base of the foramen cecum. In 4 of these 10 patients, craniotomy confirmed that there was no intracranial extension of the dermoid. Four other patients presented with sinus ostia at the base of the columella. None of these 4 patients had intracranial extension. Clinical examination and preoperative CT scans provide most of the information needed to determine the nature, course, and extent of these lesions.     

Increased numbers of P63-positive/CD117-positive cells in advanced adenoid cystic carcinoma give a poorer prognosis

ABSTRACT: ObjectivesThis study consisted of two parts. One part was to analyze the survival rates of adenoid cystic carcinoma (ACC) in Chinese and explain the difference between our data and the literature. The other was to analyze the relationship between the expression of CD117 and the histological grade and the prognosis. METHODS: A retrospective study of 80 ACC patients was performed. Clinical data were collected, and p63, CD117 were detected by immunohistochemical staining. RESULTS: Eighty patients received follow-ups 3 to 216 months after initial diagnosis. ACC occurred in the lacrimal gland (26.3%, n = 21), nasal cavity and parasinus (33.8%, n = 27) and other sites (40.0%, n = 33). The 5-year and 10-year survival rates were 66.41% and 10.16%, respectively. Over expression of CD117 was detected in p63-negative cells in 94.3% of cases and in p63-positive cells in 45.8%. The expression of CD117 in p63-positive cells was significantly associated with the histological grade (P<0.001) and prognosis (P = 0.037) in patients in the advanced stage. CONCLUSIONS: ACC had a good 5-year survival but poor 10-year survival in Chinese, which differed from the occidental data. More p63+/CD117+ cells were associated with a higher histological grade and poorer outcome.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1701457278762097.     

Association between nasal allergy and a coding variant of the Fc ε RI β gene Glu237Gly in a Japanese population

The gene for the beta-chain of the high-affinity receptor for IgE (Fc epsilon RI beta) has been proposed as a candidate gene for atopy. A coding variant Glu237Gly has been studied in various populations with asthma and atopy, and the results were controversial for association of the variant with atopy/asthma. Because nasal allergy is a more common atopic disease and shows less remission than asthma, we analyzed whether the Glu237Gly variant is correlated with nasal allergy. The study enrolled 233 patients with nasal allergy and 100 control subjects. Further, three subgroups were selected: patients with perennial nasal allergy (n=149), Japanese cedar pollinosis (n=189), and allergy to multiple allergens (n=45). The allele frequency of Gly237 in the controls and patients was 0.14 and 0.20, and the frequency of Gly237-positive subjects was 0.23 and 0.356, respectively. There was a significant association between Gly237-positivity and nasal allergy, perennial nasal allergy, Japanese cedar pollinosis, and allergy to multiple allergens. Among all 333 subjects we observed a significant relationship between Gly237 and elevated levels of serum total IgE (>250 IU/ml) and very high IgE (>1000 IU/ml). Among patients positive for a specific IgE, Gly237 was significantly associated with high IgE for house dust, mite, and Japanese cedar pollen. These results suggest that the Glu237Gly variant of the Fc epsilon RI beta gene is involved in the development of nasal allergy through the process for the production of both specific and nonspecific IgE antibodies.     

Distribution of enterotoxin genes among carriage- and infection-associated isolates of Staphylococcus aureus

AIMS: To compare the distribution of genes encoding classical and newly described enterotoxins among Staphylococcus aureus, associated with carriage and infection. METHODS AND RESULTS: Forty-five nasal isolates from carriers and 42 clinical isolates were included. The genes sea to see and seg to sei as well as sem, sen, seo and seu were tested using multiplex and conventional PCR. The most frequently found toxin genes were egc-related genes, in particular the combination seg and sei (n = 55, 63.1%), followed by sen and seu (n = 54, 62.1%), sem (n = 51, 58.6%) and seo (n = 48, 55.2%). Significant differences were found for seg and sei combination (33 of the nasal vs 22 of the infection isolates, P = 0.048) as well as for the genes sem (P = 0.004), sen (P = 0.029) and seo (P = 0.032). Regarding the classical toxin genes no significant differences between the two groups of isolates were found. CONCLUSIONS: Significant differences between infection and carriage strains were found only for the egc-related genes, which were more common in the nasal isolates. SIGNIFICANCE AND IMPACT OF THE STUDY: The egc-related enterotoxin genes seem to be more prevalent in carriage- than in infection-associated S. aureus isolates. The possible contribution of egc-related genes in determining the potential for nasal carriage requires further investigation.     

Prediction of viability of porcine neurocysticercosis with proton magnetic resonance spectroscopy: correlation with histopathology

Neurocysticercosis (NCC) is the most frequent parasitic disease of central nervous system. In our earlier study, we had observed creatine [(creatine + phosphocreatine); (tCr)] on ex vivo proton MR spectroscopy (1H MRS) in some of the cysticercus cyst fluid samples obtained from swine's brain parenchyma. In current study, swine brains of freshly slaughtered animals naturally infected with NCC were subjected to ex vivo magnetic resonance (MR) imaging on a 1.5Tesla MR system. Cysticercus cysts (n = 12) were removed from these brains and were labeled depending upon presence or absence of edema around cysts as observed on imaging. Cysticercus cyst fluid (100 microl) was subjected to different 1H MRS experiments and results were compared with histopathological examinations to look for any relationship between tCr and parameters like quantification of musculature, and cellular infiltration in wall of the parasite. Histopathology of cyst wall was categorized into two groups based on cellular characteristics and the amount of musculature. Grade I cysts (n = 5) with no or minimal inflammation and large amount of musculature showed tCr on 1H MRS. However, grade II cysts (n = 7) with profuse inflammation and less amount of musculature in the cyst wall lacked tCr. Higher amount of musculature in grade I cysts was associated with higher concentration of tCr in the cyst fluid (r2 = 0.93, P = 0.007). Creatine appears to be a marker of innocuous and viable NCC.     

Distribution of matrix metalloproteinases MMP-1, MMP-2, MMP-8 and tissue inhibitor of matrix metalloproteinases-2 in nasal polyposis and chronic rhinosinusitis

Nasal polyposis (NP), a chronic inflammatory disease of the upper airway, is a subgroup of chronic rhinosinusitis (CRS). Matrix metallo-proteinases (MMPs) and their tissue inhibitors (TIMPs) are considered to play important roles in the pathogenesis of nasal polyposis. The aim of the current study was to evaluate and compare the levels of MMP-1, MMP-2, MMP-8 and TIMP-2 in NP and CRS with normal nasal mucosa by using immunohistochemistry. Twenty-five patients with NP and fifteen patients with CRS underwent endoscopic sinus surgery. Diseased mucosal samples were obtained from ethmoidal sinuses. Control nasal mucosa (n=10) was obtained from inferior nasal turbinate. Immunohistochemistry for MMP-1, MMP-2, MMP-8 and TIMP-2 was performed. The expression of MMP-1, MMP-2 and MMP-8 significantly increased in NP and CRS compared with control (p<0.05). The distribution of TIMP-2 was higher in CRS than control and NP respectively (p<0.05). MMP-1 immunoreactivity was distributed in the extracellular matrix whereas MMP-2, MMP-8 and TIMP-2 immunostaining was present in the epithelium, submucosal glands, vascular endothelium and inflammatory cells in CRS and NP. We suggest that differences in histological features between CRS and NP might be related to the expression of MMP-1, MMP-2, MMP-8 and their tissue inhibitor-2.     

腹腔镜下卵巢囊肿剥除术中不同止血方法对卵巢良性囊肿患者卵巢功能、应激反应以及T细胞亚群的影响

目的探讨腹腔镜下卵巢囊肿剥除术中不同止血方法对卵巢良性囊肿患者应激反应、卵巢功能以及T细胞亚群的影响。方法:选取我院于2017年1月~2019年1月间接收的80例卵巢良性囊肿患者,根据随机数字表法分为A组(n=40)和B组(n=40)A组患者术中采用双极电凝止血,B组患者术中采用缝合止血,比较两组患者卵巢功能[卵泡刺激素(FSH)、雌二醇(E2)以及黄体生成素(LH)]、应激反应[促肾上腺皮质激素(ACTH)、去甲肾上腺素(NE)以及皮质醇(Cor)]、T细胞亚群及并发症发生率。结果:两组患者术后3个月FSH、LH均升高,但B组低于A组(P<0.05);E2降低,但B组高于A组(P<0.05)。两组患者术后3个月ACTH、NE、Cor均升高,但B组低于A组(P<0.05)。两组患者术后3个月CD3⁺、CD4⁺/CD8⁺、CD4⁺均降低但B组高于A组(P<0.05);CD8⁺升高,但B组低于A组(P<0.05)。两组术后并发症发生率比较差异无统计学意义(P>0.05)。结论:与双极电凝止血相比,腹腔镜下卵巢囊肿剥除术中采用缝合止血可减轻卵巢功能损害,降低应激反应,减轻免疫抑制,且不增加并发症发生率。     

Ontogenetic scaling of the human nose in a longitudinal sample: Implications for genus Homo facial evolution

Researchers have hypothesized that nasal morphology, both in archaic Homo and in recent humans, is influenced by body mass and associated oxygen consumption demands required for tissue maintenance. Similarly, recent studies of the adult human nasal region have documented key differences in nasal form between males and females that are potentially linked to sexual dimorphism in body size, composition, and energetics. To better understand this potential developmental and functional dynamic, we first assessed sexual dimorphism in the nasal cavity in recent humans to determine when during ontogeny male‐female differences in nasal cavity size appear. Next, we assessed whether there are significant differences in nasal/body size scaling relationships in males and females during ontogeny. Using a mixed longitudinal sample we collected cephalometric and anthropometric measurements from n = 20 males and n = 18 females from 3.0 to 20.0+ years of age totaling n = 290 observations. We found that males and females exhibit similar nasal size values early in ontogeny and that sexual dimorphism in nasal size appears during adolescence. Moreover, when scaled to body size, males exhibit greater positive allometry in nasal size compared to females. This differs from patterns of sexual dimorphism in overall facial size, which are already present in our earliest age groups. Sexually dimorphic differences in nasal development and scaling mirror patterns of ontogenetic variation in variables associated with oxygen consumption and tissue maintenance. This underscores the importance of considering broader systemic factors in craniofacial development and may have important implications for the study of patters craniofacial evolution in the genus Homo. Am J Phys Anthropol 153:52–60, 2014. © 2013 Wiley Periodicals, Inc.     

Metabolite pattern of Cysticercus cellulosae metacestode from different predilection sites of swine using proton magnetic resonance spectroscopy

Cysticercosis due to Taenia solium is one of the most common public health problems in various regions of the world. We have performed prolon magnetic resonance spectroscopy (1H MRS) experiments of the fluid aspirated from cysticerci excised from skeletal muscle (n = 16) and brain (n = 9) of infected swine to compare the metabolite pattern of cysticerci in different predilection sites. Perchloric acid extract of cysticercus cysts excised from skeletal muscles (n = 16) was also prepared to ascertain water-soluble, low molecular weight metabolites using 1H MRS. Absolute quantification and statistical analysis of different metabolites was done to look for any significant differences in different locations of cysts. The metabolite pattern of cysticerci was found to be similar in the various predilection sites. Metabolites observed were leucine, valine, alanine, lysine, glycine, lipid contents, lactate, glutamate, acetate, succinate, creatine, choline, and glucose. Concentration of creatine in cysticercus fluid of cysts removed from the muscle was found to be significantly higher (p = 0.001) than the cysts located in the brain. We conclude that the metabolite pattern in the cysticerci is not influenced by the surrounding tissue location; however concentration of certain metabolites may depend upon the tissue location.     

The nasal dorsum as a donor site for the correction of alar, lobular, and columellar malformations

There is a wide variety of donor sites available for minor nasal reconstructions involving alar, lobular, and columellar defects. Unfortunately, the problems all these sites have in common are that the color match may be unsatisfactory or that the end result may be marred by conspicuous scarring. If nasal-skin resources could be fully exploited, the elimination of these two important problems could become an obtainable goal.This article discusses the potential of the nasal dorsum as a donor site and describes methods that were used to try to achieve this goal. Skin redistribution, skin expansion, and skin distraction methods were used in 28 patients with alar (n = 13), lobular (n = 8), and columellar (n = 7) malformations and who had been followed up since the early 1980s.     

Growth and survival of vascularized and nonvascularized membranous bone: an experimental study

Although nonvascularized membranous bone grafts to the craniofacial skeleton demonstrate improved survival over similar grafts of endochondral origin, the comparative fate of vascularized membranous grafts is unknown. It is also unknown whether onlay membranous bone grafts in immature animals have the ability to grow. To examine these questions, a model was developed in New Zealand white rabbits in which a segment of the zygomatic arch was transferred to the subjacent mandible as either a vascularized or nonvascularized transfer. At harvest 16 weeks later, residual graft volume and bone architecture were analyzed. Results demonstrate no improved survival for vascularized membranous grafts in adult animals (n = 7), while in the immature animals (n = 6), growth of the vascularized bone transfers was documented. We conclude that in the majority of instances in craniofacial reconstruction, nonvascularized onlay membranous grafts are to be preferred. Specific instances for the use of vascularized transfers will be discussed.     

Mast cells in human odontogenic cysts

Abstract

Mast cells are granule-containing cells in mucosal and connective tissues that are known to play a central role in allergic and inflammatory responses owing to pro-inflammatory mediators. Cysts in jaws are among the most common expansive, benign and destructive bone lesions; at some stage they are associated with chronic inflammation. Earlier studies have identified mast cells in odontogenic cysts (OC). We investigated the presence and distribution of mast cells and compared their number in different types of radicular cysts (RC), dentigerous cysts (DC) and odontogenic keratocysts (OKC). Ten cases each of RC, DC and OKC diagnosed clinically and histopathologically were selected and stained with 1% toluidine blue. The greatest number of mast cells/mm² was found in RC. The fewest mast cells/mm² were found in OKC. The subepithelial zones of all cysts contained more mast cells than the deeper zones.     

Sites of origin and patterns of migration of vasotocin/mesotocin neurons in developing brain of the chick

Vasotocin/mesotocin (VT/MT) producing neurons are known to migrate extensively during development of the hypothalamus. Birthdating studies as well as immunohistochemical studies suggested the possibility that VT/MT producing neurons originate from specific sites of the neural tube. Furthermore, a relationship between the site of origin and the eventual fate of VT/MT cells has been suggested. This study proposes to identify the sites of origin of VT/MT cells and to establish whether magnocellular and parvocellular VT/MT, and neuromodulatory and neurosecretory VT/MT arise from common or different areas of the developing neural tube. To do so, the embryological distribution of VT/MT producing neurons of the chick was studied with immunohistochemistry. Analysis of the youngest brains in which VT/MT cells could be detected (embryonic day 7.25, E7.25) suggested the presence of two separate sites of origin. The first site was located in the hypothalamic anlage, next to the third ventricle, and the second in the mesencephalon, next to the fourth ventricle. Three-dimensional reconstructions of the location of VT/MT cells throughout development substantiated the hypothesis that diencephalic VT/MT cells originate from the first site while mesencephalic ones originate from the second site. Mesencephalic VT/MT producing cells were confined to the nucleus of Edinger-Westphal and were only detectable during a brief period in development (E7.25–E10). Diencephalic VT/MT producing neurons were noted to form two main paths from their site of origin to the rostral diencephalon. Quantitative analysis confirmed this caudal to rostral displacement. Magnocellular and parvocellular VT/MT+ cells were intermingled at the diencephalic site of origin as well as in the migratory paths. Neuromodulatory and neurosecretory VT/MT cells of the diencephalon appeared to be derived from a common diencephalic site of origin. These studies support the hypothesis that while specific groups of progenitors may be important in allowing their offspring to produce VT/MT, they do not appear to influence the morphological attributes (magnocellular vs. parvocellular), nuclear locations, or functional characteristics of these cells. © 1996 John Wiley & Sons, Inc.     

Postrhinoplasty nasal cysts and the use of petroleum-based ointments and nasal packing

Nasal cysts are rare complications of rhinoplasty, and numerous theories exist regarding their cause. The term "paraffinoma" has been used to describe cyst formation observed after topical antibiotic ointment application with nasal packing in the immediate postoperative period. Such complications are rare but may occur because of the inherent properties of the agent used or a lack of meticulous technique (in the placement of incisions and nasal packing). Three cases of postrhinoplasty cysts with a variety of presentations, including incidental intraoperative findings, bilateral medial canthal masses, and a draining dorsal cyst, are described. Although such cysts are uncommon, techniques to prevent these unwanted sequelae should routinely be used, with the judicious application of non-petroleum-based topical antibiotic preparations.