Search

This interdisciplinary study examined the relationship between bone density and drilling forces required during trans-pedicular access to the vertebra using fresh–frozen thoraco-lumbar vertebrae from two female body donors (A, B). Before and after biomechanical examination, samples underwent high-resolution CT-quantification of total bone density followed by software-based evaluation and processing. CT density measurements (n = 4818) were calculated as gray values (GV), which were highest in T12 for both subjects (GVmaxA = 3483.24, GVmaxB = 3160.33). Trans-pedicular drilling forces F (Newton N) were highest in L3 (FmaxB = 5.67 N) and L4 (FmaxA = 5.65 N). In 12 out of 13 specimens, GVs significantly (p < 0.001) correlated with force measurements. Among these, Spearman correlations r were poor in two lumbar vertebrae, fair in five specimens, and moderately strong in another five specimens, and highest for T11 (rA = 0.721) and L5 (rB = 0.690). Our results indicate that CT-based analysis of vertebral bone density acquired in anatomical specimens is a promising approach to predict the drilling force appearance as surrogate parameter of its biomechanical properties by e.g., linear regression analysis. The study may be of value as basis for biomechanical investigations to improve planning of the optimal trajectory and to define safety margins for drilling forces during robotic-assisted trans-pedicular interventions on the spine in the future. [ABSTRACT FROM AUTHOR]

The presented course, established 2016 as a compulsory elective for 22nd‐year bachelor medical students, aimed to enhance deep learning of upper and lower limb anatomy from a clinical perspective by a maximum of student‐centered activities combining hands‐on skills training with team‐learning. Three cohorts (in total 60 students) participated in this study. Students rotated through body painting, ultrasound, and clinical investigation supervised by faculty or an experienced clinician. Teams of 3‐4 students prepared presentations on clinical anatomy and pathological conditions, which by teacher‐ and peer assessments on average achieved >85% (mean 17.8/20 points ± 1.06). After each activity session, the students reported their learning experience through a reflective diary. Fifty students (83%) evaluated the course by a voluntary anonymous questionnaire combining Likert‐type scale and free‐text questions to assess, predominantly, perception of course activities and their perceived influence on learning anatomy. Journal reports and questionnaires revealed that the students highly valued the course, and 92% (29 females, 17 males) rated group work satisfying or well‐perceived. The highest appreciation achieved ultrasound followed by clinical examination and body painting, which one third proposed to integrate into the regular dissection course. All students recommended the course to their younger peers. This course was feasible to integrate in the pre‐existing curriculum. Limiting factors to offer this elective course to more students are availability of clinical teachers, technical equipment, and education rooms. Being student‐directed tasks, body painting and reflective diary‐writing would be feasible to implement without additional faculty, which we recommend to educators for student engagement activation. [ABSTRACT FROM AUTHOR]

Background: Thiel-fixed body donors are highly valued for surgical training courses. The pronounced flexibility of Thiel-fixed tissue has been postulated to be caused by histologically visible fragmentation of striated muscle. The aim of this study was to analyse whether a specific ingredient, pH, decay, or autolysis could cause this fragmentation in order to modulate the Thiel solution to adapt specimen flexibility specifically to the needs of different courses. Materials and methods: Striated muscle of the mouse was fixed for different time periods in formalin, Thiel solution, and its individual ingredients, and analysed by light microscopy. Further, pH-values of Thiel solution and its ingredients were measured. In addition, unfixed muscle tissue was histologically analysed including Gram staining to investigate a relationship between autolysis, decomposition, and fragmentation. Results: Muscle fixed with Thiel solution for 3 months was slightly more fragmentated than muscle fixed for 1 day. Fragmentation was more pronounced after 1 year of immersion. Three individual salt ingredients showed slight fragmentation. Decay and autolysis had no effect on fragmentation, which occurred regardless of the pH of all solutions. Conclusions: Fragmentation of Thiel-fixed muscle is dependent on fixation time and most likely occurs due to salts present in the Thiel solution. Adjustment of the salt composition in the Thiel solution with verification of the influence on the fixation effect, fragmentation and flexibility of the cadavers could be performed in further studies. [ABSTRACT FROM AUTHOR]

Prolactin (Prl) and growth hormone (Gh) as well as insulin-like growth factor 1 (Igf1) are involved in the physiological adaptation of fish to varying salinities. The Igfs have been also ascribed other physiological roles during development, growth, reproduction and immune regulation. However, the main emphasis in the investigation of osmoregulatory responses has been the endocrine, liverderived Igf1 route and local regulation within the liver and osmoregulatory organs. Few studies have focused on the impact of salinity alterations on the Gh/Igf-system within the neuroendocrine and immune systems and particularly in a salinity-tolerant species, such as the blackchin tilapia Sarotherodon melanotheron. This species is tolerant to hypersalinity and saline variations, but it is confronted by severe climate changes in the Saloum inverse estuary. Here we investigated bidirectional effects of increased salinity followed by its decrease on the gene regulation of prl, gh, igf1, igf2, Gh receptor and the tumor-necrosis factor a. A mixed population of sexually mature 14-month old blackchin tilapia adapted to freshwater were first exposed to seawater for one week and then to fresh water for another week. Brain, pituitary, head kidney and spleen were excised at 4 h, 1, 2, 3 and 7 days after both exposures and revealed differential expression patterns. This investigation should give us a better understanding of the role of the Gh/Igf system within the neuroendocrine and immune organs and the impact of bidirectional saline challenges on fish osmoregulation in non-osmoregulatory organs, notably the complex orchestration of growth factors and cytokines. [ABSTRACT FROM AUTHOR]

Background: For optimal prosthetic anchoring in omarthritis surgery, a differentiated knowledge on the mineralisation distribution of the glenoid is important. However, database on the mineralisation of diseased joints and potential relations with glenoid angles is limited.Methods: Shoulder specimens from ten female and nine male body donors with an average age of 81.5 years were investigated. Using 3D-CT-multiplanar reconstruction, glenoid inclination and retroversion angles were measured, and osteoarthritis signs graded. Computed Tomography-Osteoabsorptiometry (CT-OAM) is an established method to determine the subchondral bone plate mineralisation, which has been demonstrated to serve as marker for the long-term loading history of joints. Based on mineralisation distribution mappings of healthy shoulder specimens, physiological and different CT-OAM patterns were compared with glenoid angles.Results: Osteoarthritis grades were 0-I in 52.6% of the 3D-CT-scans, grades II-III in 34.3%, and grade IV in 13.2%, with in females twice as frequently (45%) higher grades (III, IV) than in males (22%, III). The average inclination angle was 8.4°. In glenoids with inclination ≤10°, mineralisation was predominantly centrally distributed and tended to shift more cranially when the inclination raised to > 10°. The average retroversion angle was - 5.2°. A dorsally enhanced mineralisation distribution was found in glenoids with versions from - 15.9° to + 1.7°. A predominantly centrally distributed mineralisation was accompanied by a narrower range of retroversion angles between - 10° to - 0.4°.Conclusions: This study is one of the first to combine CT-based analyses of glenoid angles and mineralisation distribution in an elderly population. The data set is limited to 19 individuals, however, indicates that superior inclination between 0° and 10°-15°, and dorsal version ranging between - 9° to - 3° may be predominantly associated with anterior and central mineralisation patterns previously classified as physiological for the shoulder joint. The current basic research findings may serve as basic data set for future studies addressing the glenoid geometry for treatment planning in omarthritis. [ABSTRACT FROM AUTHOR]

Introduction: This pilot study explores whether a human Thiel-embalmed temporal bone is suitable for generating an accurate and complete data set with micro-computed tomography (micro-CT) and whether solid iodine-staining improves visualization and facilitates segmentation of middle ear structures. Methods: A temporal bone was used to verify the accuracy of the imaging by first digitally measuring the stapes on the tomography images and then physically under the microscope after removal from the temporal bone. All measurements were compared with literature values. The contralateral temporal bone was used to evaluate segmentation and three-dimensional (3D) modeling after iodine staining and micro-CT scanning. Results: The digital and physical stapes measurements differed by 0.01–0.17 mm or 1–19%, respectively, but correlated well with the literature values. Soft tissue structures were visible in the unstained scan. However, iodine staining increased the contrast-to-noise ratio by a factor of 3.7 on average. The 3D model depicts all ossicles and soft tissue structures in detail, including the chorda tympani, which was not visible in the unstained scan. Conclusions: Micro-CT imaging of a Thiel-embalmed temporal bone accurately represented the entire anatomy. Iodine staining considerably increased the contrast of soft tissues, simplified segmentation and enabled detailed 3D modeling of the middle ear. [ABSTRACT FROM AUTHOR]

This educational study aimed to explore the feasibility and acceptance of a literacy exercise adopted from the realworld of scientific publishing in a cell and tissue biology course. For that purpose, a tertiary-level multimodality science course, which integrated a blended learning faculty and student lectures, journal club, and wet laboratory sessions including a research project as well as examinations, was complemented by essaywriting of a review and peerreviewing of five manuscripts. All tasks contributed to the final course mark. Special emphasis was laid on the usability of different E-Learning applications for scientific writing and teacher- and peerassessment procedures. Further, potential influences of student characteristics on their peer- and self-assessments as well as their acceptance of the feedback from their peers were evaluated. Seventy-five undergraduate students from different Bachelor programs were included in the study. Plagiarism check and double-blind assessments of the essays were performed using "Turnitin.com." Students self-assessed their paper and received feedback from five peers and the teacher. Peer assessment was more severe than the teacher- or self-assessment, and the peer mark correlated best with the final course mark. Students with better marks assessed more generously, and there had moderate tendencies for influences of gender and background on peer feedback behavior. The students perceived the writing and assessment exercises, especially being peer-assessed, as demanding, but rewarding and a great learning experience. The additional tasks were feasible using E-Learning technology, which should foster future biomedical courses to train writing skills and the ability to cope with different roles in the scientific community. [ABSTRACT FROM AUTHOR]

The autonomic nerves of the lesser pelvis are particularly prone to iatrogenic lesions due to their exposed position during manifold surgical interventions. Nevertheless, the cause of rectal and urinary incontinence or sexual dysfunctions, for example after rectal cancer resection or hysterectomy, remains largely understudied, particularly with regard to the female pelvic autonomic plexuses. This study focused on the macroscopic description of the superior hypogastric plexus, hypogastric nerves, inferior hypogastric plexus, the parasympathetic pelvic splanchnic nerves and the sympathetic fibres. Their arrangement is described in relation to commonly used surgical landmarks such as the sacral promontory, ureters, uterosacral ligaments, uterine and rectal blood vessels. Thirty‐one embalmed female pelvises from 20 formalin‐fixed and 11 Thiel‐fixed cadavers were prepared. In all cases explored, the superior hypogastric plexus was situated anterior to the bifurcation of the abdominal aorta. In 60% of specimens, it reached the sacral promontory, whereas in 40% of specimens, it continued across the pelvic brim until S1. In about 25% of the subjects, we detected an accessory hypogastric nerve, which has not been systematically described so far. It originated medially from the inferior margin of the superior hypogastric plexus and continued medially into the presacral space. The existence of an accessory hypogastric nerve was confirmed during laparoscopy and by histological examination. The inferior hypogastric plexuses formed fan‐shaped plexiform structures at the end of both hypogastric nerves, exactly at the junction of the ureter and the posterior wall of the uterine artery at the uterosacral ligament. In addition to the pelvic splanchnic nerves from S2–S4, which joined the inferior hypogastric plexus, 18% of the specimens in the present study revealed an additional pelvic splanchnic nerve originating from the S1 sacral root. In general, form, breadth and alignment of the autonomic nerves displayed large individual variations, which could also have a clinical impact on the postoperative function of the pelvic organs. The study serves as a basis for future investigations on the autonomic innervation of the female pelvic organs. [ABSTRACT FROM AUTHOR]

Profound anatomical knowledge is the basis for modern demands in medicine and surgery, but many countries worldwide including Australia and New Zealand have discontinued offering dissection courses to medical and dental students during the past decades. This educational project done in Australia aimed at enhancing basic and advanced anatomy teaching by engaging a sub-group of second-year undergraduate students of a compulsory prosection- and model-based anatomy course ( n = 54/170) in an optional multimodal course, which should easily articulate with a vertical curriculum. With topographical cadaver dissections as core, peer student-teams prepared and peer-assessed anatomy lectures based on clinical topics, which were rated highly by the peers and teachers. Anatomical knowledge was tested by quizzes and a multiple-choice examination. Individual dissection skills were self- and teacher-assessed. A final course grade was assigned based on these assessments. The grades in the system-based compulsory course achieved by the attendees of the paralleling dissection course were compared with their peers attending other optional courses. After beginning of the semester, the students in the dissection course performed similar, significantly ( P < 0.005) improved during the semester (78.5% vs. 69.9%, 70.1% vs. 64.1%), but in the integrated (including anatomy, biochemistry, physiology) final examination at the end of the year only tended to higher scores. As assessed through interviews and a voluntary questionnaire, all students of the optional dissection course liked these activities, which enhanced their learning experience. Thus, this concept elegantly integrates anatomical dissection with modern teaching demands and is feasible for implementation in modernized curricula. Anat Sci Educ 11: 32-43. © 2017 American Association of Anatomists. [ABSTRACT FROM AUTHOR]

Background: Placement of the glenoid baseplate is of paramount importance for the outcome of anatomical and reverse total shoulder arthroplasty. However, the database around glenoid size is poor, particularly regarding small scapulae, for example, in women and smaller individuals, and is derived from different methodological approaches. In this multimodality cadaver study, we systematically examined the glenoid using morphological and 3D-CT measurements.Methods: Measurements of the glenoid and drill hole tunnel length for superior baseplate screw placement were recorded to define size of the glenoid and the distance to the scapular notch on cadaveric specimens. Glenoid angles were determined on both, 3D-CT-scans of the thoraxes using the Friedman method and on subsequently isolated scapulae from 18 male and female donors (average 84 years, range 60-98 years).Results: Mean glenoid height was 36.6 mm ± 3.6, and width 27.8 mm ± 3.1 with a significant sex dimorphism (p ≤ 0.001): in males, glenoid height 39.5 mm ± 3.5, and width 30.3 mm ± 3.3, and in females, glenoid height 34.8 mm ± 2.2, and width 26.2 mm ± 1.6. The average distance from the superior screw entry to its exit in the scapular notch measured by calliper was 27.2 mm ± 6.0 with a sex difference: in males, 29.4 mm ± 5.7, and in females, 25.8 mm ± 5.9 mm with a minimum recorded distance of 15 mm. Measured by CT, the mean inclination angle for male and female donors combined was 13.0° ± 7.0, and the ante-/retroversion angle -1.0° ± 4.0°.Conclusion: This study is one of the first to combine dissection, including drill holes, with anatomical measurements and radiological data. In some women and smaller individuals, smaller baseplates should be selected. The published safe zone of 20 mm is generally feasible for superior screw placement, however, in small patients this distance may be substantially shorter than expected and start as of 13 and 15 mm, respectively. No correlation between glenoid height or width with the length of our drilling canal towards the scapular notch was found. Preoperative CT-based treatment planning to determine version and inclination angles is recommended. [ABSTRACT FROM AUTHOR]

A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived), which has also been shown to be suppressed during infection in some studies. Nevertheless, data are still fragmentary. Some studies point to an important role of GH and IGF-I particularly during immune organ development and constitution. Even less is known about the potential relevance of local (autocrine/paracrine) IGF-I within adult and developing immune organs, and the distinct localization of IGF-I in immune cells and tissues of mammals and fish has not been systematically defined. Thus far, IGF-I has been localized in different mammalian immune cell types, particularly macrophages and granulocytes, and in supporting cells, but not in T-lymphocytes. In the present study, we detected IGF-I in phagocytic cells isolated from rainbow trout head kidney and, in contrast to some findings in mammals, in T-cells of a channel catfish cell line. Thus, although numerous analogies among mammals and teleosts exist not only for the GH/IGF-system, but also for the immune system, there are differences that should be further investigated. For instance, it is unclear whether the primarily reported role of GH/IGF-I in the innate immune response is due to the lack of studies focusing on the adaptive immune system, or whether it truly preferentially concerns innate immune parameters. Infectious challenges in combination with GH/IGF-I manipulations are another important topic that has not been sufficiently addressed to date, particularly with respect to developmental and environmental influences on fish growth and health. [ABSTRACT FROM AUTHOR]

Hodgkin's lymphoma (HL) is among the most frequent nodal lymphomas in the Western world and is classified into two disease entities: nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) and classical Hodgkin's lymphoma (cHL, 95 % of all HL). HL lesions are characterised by a minority of clonal neoplastic cells, namely Hodgkin and Reed-Sternberg (HRS) cells and their variants in cHL and lymphocyte-predominant (LP) cells in NLPHL, both occurring within a microenvironment of, for example, reactive T and B cells, macrophages and granulocytes that are assumed to support the proliferation and maintenance of neoplastic cells through cytokines, chemokines and growth factors. Insulin-like growth factor I (IGF-I) is an important growth factor involved in proliferation, differentiation, apoptosis and cell survival of numerous (including immune) tissues and probably has a role in tumour pathogenesis and maintenance. Although HL is characterised by disturbed cell differentiation and apoptosis mechanisms, with the involvement of the IGF-I receptor (IGF-1R), the distinct location of IGF-I in HL has not yet been defined. We localise IGF-I by double-immunofluorescence in frequent neoplastic cells of all cHL and NLPHL cases investigated. Additionally, IGF-I immunoreactivity is detected in high endothelial venules and various immune cells within the surrounding tissue of cHL including neutrophils and macrophages. IGF-1R immunoreactivity of variable intensity is found in HRS cells and high endothelial venules within the microenvironment in cHL. We assume that autocrine and paracrine IGF-I plays an anti-apoptotic role in tumour pathogenesis and in shaping the tumour microenvironment. [ABSTRACT FROM AUTHOR]

Objective: For human scapulae, we have described a significant sexual dimorphism. However, when it comes to correlation with body size, the database is still weak, particularly for women and smaller sized individuals. Previous studies from our group revealed contradictory results for the correlation of upper limb dimensions to body size. Furthermore, in the elderly, potential osteoporotic compression fractures have to be considered. Thus, there is a demand to compare scapula dimensions with body size in a larger data set with special emphasis on aged and female individuals. Methods: Computed tomography (CT) scans were performed prior to dissection on human body donors and included the shoulder girdle and arms. Shoulder parameters were measured on subsequently isolated scapulae and by 3D-CT reconstructions of the gleno-humeral joint performed according to Friedman. Body height was determined using different methodological approaches and correlated to scapula size to create a data set in the elderly with special emphasis on women. The project was approved by the cantonal ethics committee. Results: In this multimodality study, we establish a morphological and CT-based data set of the gleno-humeral joint in human body donors, which serves to compare and extrapolate scapula and body sizes also in other specimens to be later expanded to include more individuals. Conclusion: We aim at establishing a systematic basis of scapula parameters and body sizes for future studies in physiology, comparative and translational research and in diverse pathologies. [ABSTRACT FROM AUTHOR]

Calcified dental plaque (dental calculus) preserves for millennia and entraps biomolecules from all domains of life and viruses. We report the first, to our knowledge, high-resolution taxonomic and protein functional characterization of the ancient oral microbiome and demonstrate that the oral cavity has long served as a reservoir for bacteria implicated in both local and systemic disease. We characterize (i) the ancient oral microbiome in a diseased state, (ii) 40 opportunistic pathogens, (iii) ancient human-associated putative antibiotic resistance genes, (iv) a genome reconstruction of the periodontal pathogen Tannerella forsythia, (v) 239 bacterial and 43 human proteins, allowing confirmation of a long-term association between host immune factors, 'red complex' pathogens and periodontal disease, and (vi) DNA sequences matching dietary sources. Directly datable and nearly ubiquitous, dental calculus permits the simultaneous investigation of pathogen activity, host immunity and diet, thereby extending direct investigation of common diseases into the human evolutionary past. [ABSTRACT FROM AUTHOR]

Exercise, obesity and type 2 diabetes are associated with elevated plasma concentrations of interleukin-6 (IL-6). Glucagon-like peptide-1 (GLP-1) is a hormone that induces insulin secretion. Here we show that administration of IL-6 or elevated IL-6 concentrations in response to exercise stimulate GLP-1 secretion from intestinal L cells and pancreatic alpha cells, improving insulin secretion and glycemia. IL-6 increased GLP-1 production from alpha cells through increased proglucagon (which is encoded by GCG) and prohormone convertase 1/3 expression. In models of type 2 diabetes, the beneficial effects of IL-6 were maintained, and IL-6 neutralization resulted in further elevation of glycemia and reduced pancreatic GLP-1. Hence, IL-6 mediates crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand. This previously unidentified endocrine loop implicates IL-6 in the regulation of insulin secretion and suggests that drugs modulating this loop may be useful in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Several lines of GH-overexpressing fish have been produced and characterized concerning organ integrity, growth, fertility and health but few and contradictory data are available on IGF-I that mediates most effects of GH. Furthermore, nothing is known on IGF-II. Thus, the expression of both IGFs in liver and various extrahepatic sites of adult transgenic (GH-overexpressing) tilapia and age-matched wild-type fish was determined by real-time PCR. Both IGF-I and IGF-II mRNA were found in all organs investigated and were increased in gills, kidney, intestine, heart, testes, skeletal muscle and brain of the transgenics (IGF-I: 1.4-4-fold; IGF-II: 1.7-4.2-fold). Except for liver, brain and testis the increase in IGF-I mRNA was higher than that in IGFII mRNA. In pituitary, no significant change in IGF-I or IGF-II mRNA was detected. In spleen, however, IGF-I and IGF-II mRNA were both decreased in the transgenics, IGF-I mRNA even by the 19-fold. In agreement, in situ hybridisation revealed a largely reduced number of IGF-I mRNA-containing leukocytes and macrophages when compared to wild-type. These observations may contribute to better understanding the reported impaired health of GH-transgenic fish. Growth enhancement of the transgenics may be due to the increased expression of both IGF-I and IGF-II in extrahepatic sites. It is also reasonable that the markedly enhanced expression of liver IGF-II mRNA that may mimick an early developmental stage is a further reason for increased growth. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor I (IGF-I) is a potent hormone that stimulates growth and differentiation and inhibits apoptosis in numerous tissues. Preliminary evidence suggests that IGF-I exerts differentiating, mitogenic and restoring activities in the immune system but the sites of synthesis of local IGF-I are unknown. Identification of these sites would allow the functional role of local IGF-I to be clarified. The presence of IGF-I in non-immune cells suggests that it acts as a trophic factor, while its occurrence in subtypes of lymphocytes or antigen-presenting cells indicates paracrine/autocrine direct regulatory involvement of IGF-I in the human immune response. The present study investigated the location of IGF-I messenger RNA and protein on archival human lymph node samples by in situ hybridization, immunohistochemistry and double immunofluorescence staining using an IGF-I probe and antisera specific for human IGF-I and CD3 (T lymphocytes), CD20 (B lymphocytes), CD68 (macrophages), CD21 (follicular dendritic cells), S100 (interdigitating dendritic cells) and podoplanin (fibroblastic reticular cells). Numerous cells within the B- and T-cell compartments expressed the IGF-I gene, and the majority of these cells were identified as macrophages. Solitary follicular dendritic cells exhibited IGF-I. A few T lymphocytes, and no B lymphocytes, contained IGF-I immunoreactive material. Furthermore, IGF-I immunoreactive cells outside the follicles that did not react with CD3, CD20, S100 or podoplanin markers were identified as high-endothelial venule (HEV) cells. From this we conclude that the main task of IGF-I in human non-tumoral lymph node may be autocrine and paracrine regulation of the differentiation, stimulation and survival of lymphocytes, antigen-presenting cells and macrophages and the differentiation and maintenance of HEV cells. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor (IGF)-I, which is crucially involved in fish growth, differentiation, and reproduction, occurs in tilapia pituitary. IGF-I peptide, which is probably produced in hypothalamic perikarya, is present in axons of the neurohypophysis, and IGF-I mRNA and peptide are present in the adenohypophysis in adrenocorticotrophic hormone cells, melanocyte-stimulating hormone cells, with interindividual differences in growth hormone cells, and, starting with puberty, in gonadotrophic hormone (GTH) cells. Subordinate males showed a high IGF-I but a lower β-luteinizing hormone expression, while in dominant males the opposite was found. IGF-I from the GTH cells may act as auto/paracrine regulators of GTH cell proliferation and enhance GTH synthesis and release during puberty and reproduction, depending on the social status. [ABSTRACT FROM AUTHOR]

Activation of the innate immune system in obesity is a risk factor for the development of type 2 diabetes. The aim of the current study was to investigate the notion that increased numbers of macrophages exist in the islets of type 2 diabetes patients and that this may be explained by a dysregulation of islet-derived inflammatory factors. Increased islet-associated immune cells were observed in human type 2 diabetic patients, high-fat--fed C57BL/6J mice, the GK rat, and the db/db mouse. When cultured islets were exposed to a type 2 diabetic milieu or when islets were isolated from high-fat--fed mice, increased islet-derived inflammatory factors were produced and released, including interleukin (IL)-6, IL-8, chemokine KC, granulocyte colony-stimulating factor, and macrophage inflammatory protein 1α. The specificity of this response was investigated by direct comparison to nonislet pancreatic tissue and β-cell lines and was not mimicked by the induction of islet cell death. Further, this inflammatory response was found to be biologically functional, as conditioned medium from human islets exposed to a type 2 diabetic milieu could induce increased migration of monocytes and neutrophils. This migration was blocked by IL-8 neutralization, and IL-8 was localized to the human pancreatic α-cell. Therefore, islet-derived inflammatory factors are regulated by a type 2 diabetic milieu and may contribute to the macrophage infiltration of pancreatic islets that we observe in type 2 diabetes. Diabetes 56:2356-2370, 2007 [ABSTRACT FROM AUTHOR]

Few and controversial results exist on the cellular sites of insulin-like growth factor (IGF)-I synthesis and the type 1 IGF receptor (IGF-1R) in mammalian anterior pituitary. Thus, the present study analysed IGF-I and the IGF-1R in rat pituitary. Reverse transcription-polymerase chain reaction revealed IGF-I and IGF-1R mRNA expression in pituitary. The sequences of both were identical to the corresponding sequences in other rat organs. In situ hybridization localized IGF-I mRNA in endocrine cells. The majority of the growth hormone (GH) cells and numerous adrenocorticotropic hormone (ACTH) cells exhibited IGF-1R-immunoreactivity at the cell membrane. At lower densities, IGF-1 receptors were also present at the other hormone-producing cell types, indicating a physiological impact of IGF-I for all endocrine cells. IGF-I-immunoreactivity was located constantly in almost all ACTH-immunoreactive cells. At the ultrastructural level, IGF-I-immunoreactivity was confined to secretory granules in co-existence with ACTH-immunoreactivity, indicating a concomitant release of both hormones. Occasionally, IGF-I-immunoreactivity was detected in an interindividually varying number of GH cells. In some individuals, weak IGF-I-immunoreactions were also detected also in follicle-stimulating hormone and luteinizing hormone cells. Thus, IGF-I seems to be produced as a constituent in ACTH cells, possibly indicating its particular importance in stress response. Generally, IGF-I from the endocrine cells may regulate synthesis and/or release of hormones in an autocrine/paracrine manner as well as prevent apoptosis and stimulate proliferation. Production of IGF-I in GH cells may depend on the physiological status, most likely the serum IGF-I level. IGF-I released from GH cells may suppress GH synthesis and/or release by an autocrine feedback mechanism in addition to the endocrine route. [ABSTRACT FROM AUTHOR]

Fish pituitary plays a central role in the control of growth, development, reproduction and adaptation to the environment. Several types of hormone–secreting adenohypophyseal cells have been characterised and localised in diverse teleost species. The results suggest a similar distribution pattern among the species investigated. However, most studies deal with a single hormone or hormone family. Thus, we studied adjacent sections of the pituitary of Oreochromis niloticus, the tilapia, by conventional staining and immunohistochemistry with specific antisera directed against growth hormone (GH), prolactin (PRL), somatolactin (SL), thyrotropin (β–TSH), follicle–stimulating hormone (β–FSH), luteinising hormone (β–LH), adrenocorticotropic hormone (ACTH) and melanocyte–stimulating hormone (α–MSH). The pituitary was characterised by a close interdigitating neighbourhood of neurohypophysis (PN) and adenohypophysis. PRL–immunoreactive and ACTH–immunoreactive cells were detected in the rostral pars distalis. GH–immunoreactive cells were present in the proximal pars distalis (PPD). A small region of the PPD contained β–TSH–immunoreactive cells, and β–LH–immunoreactive cells covered approximately the remaining parts. Centrally, β–FSH–immunoreactive cells were detected in the vicinity of the GH–containing cells. Some of these cells also displayed β–LH immunoreactivity. The pars intermedia was characterised by branches of the PN surrounded by SL–containing and α–MSH–immunoreactive cells.The ACTH and α–MSH antisera were observed to cross-react with the respective antigens. This cross–reactivity was abolished by pre–absorption. We present a complete map of the distinct localisation sites for the classical pituitary hormones, thereby providing a solid basis for future research on teleost pituitary. [ABSTRACT FROM AUTHOR]

The cellular sites of insulin-like growth factor I (IGF-I) synthesis in the early developing tilapia (0-140 days post fertilization, DPF) were investigated. IGF-I mRNA and peptide appeared in liver as early as 4 DPF and in gastro-intestinal epithelial cells between 5-9 DPF. In exocrine pancreas, the expression of IGF-I started at 4 DPF and continued until 90 DPF. IGF-I production was detected in islets at 6 DPF in non-insulin cells and occurred throughout life. In renal tubules and ducts, IGF-I production started at 8 DPF. IGF-I production in chondrocytes had its onset at 4 DPF, was more pronounced in growing regions and was also found in adults. IGF-I mRNA and peptide appeared in the cytoplasm of skeletal muscle cells at 4 DPF. In gill chloride cells, IGF-I production started at 6 DPF. At 13 DPF, IGF-I was detected in cardiac myocytes. IGF-I-producing epidermal cells appeared at 5 DPF. In brain and ganglia, IGF-I was expressed in virtually all neurones from 6 to 29 DPF, their number decreasing with age. Neurosecretory IGF-I-immunoreactive axons were first seen in the neurohypophysis around 17 DPF. Endocrine cells of the adenohypophysis exhibited IGF-I mRNA at 28 DPF and IGF-I immunoreactivity at 40 DPF. Thus, IGF-I appeared early (4-5 DPF), first in liver, the main source of endocrine IGF-I, and then in organs involved in growth or metabolism. The expression of IGF-I was more pronounced during development than in juvenile and adult life. Local IGF-I therefore seems to have a high functional impact in early growth, metabolism and organogenesis. [ABSTRACT FROM AUTHOR]

A decrease in the number of functional insulin-producing beta-cells contributes to the pathophysiology of type 2 diabetes. Opinions diverge regarding the relative contribution of a decrease in beta-cell mass versus an intrinsic defect in the secretory machinery. Here we review the evidence that glucose, dyslipidemia, cytokines, leptin, autoimmunity, and some sulfonylureas may contribute to the maladaptation of beta-cells. With respect to these causal factors, we focus on Fas, the ATP-sensitive K+ channel, insulin receptor substrate 2, oxidative stress, nuclear factor-kappaB, endoplasmic reticulum stress, and mitochondrial dysfunction as their respective mechanisms of action. Interestingly, most of these factors are involved in inflammatory processes in addition to playing a role in both the regulation of beta-cell secretory function and cell turnover. Thus, the mechanisms regulating beta-cell proliferation, apoptosis, and function are inseparable processes. [ABSTRACT FROM AUTHOR]

A decrease in the number of functional insulin-producing β-cells contributes to the pathophysiology of type 2 diabetes. Opinions diverge regarding the relative contribution of a decrease in β-cell mass versus an intrinsic defect in the secretory machinery. Here we review the evidence that glucose, dyslipidemia, cytokines, leptin, autoimmunity, and some sulfonylureas may contribute to the maladaptation of β-cells. With respect to these causal factors, we focus on Fas, the ATP-sensitive K+ channel, insulin receptor substrate 2, oxidative stress, nuclear factor-κB, endoplasmic reticulum stress, and mitochondrial dysfunction as their respective mechanisms of action. Interestingly, most of these factors are involved in inflammatory processes in addition to playing a role in both the regulation of β-cell secretory function and cell turnover. Thus, the mechanisms regulating β-cell proliferation, apoptosis, and function are inseparable processes. Diabetes 54 (Suppl. 2):S108-S113, 2005 [ABSTRACT FROM AUTHOR]

We have developed a real-time RT-PCR that absolutely quantifies the gene expression of hormones using the standard curve method. The method avoids cloning procedures by using primer extension to create templates containing a T7 promoter gene sequence. It is rapid since neither separate reverse transcriptions nor postamplification steps are necessary, and its low detection level (2 pg/μg total RNA) allows precise absolute quantification. Using the method, we have quantified the gene expression of GH, IGF-I, and IGF-II in the tilapia. [ABSTRACT FROM AUTHOR]

The growth arrest after hypophysectomy in rats is mainly due to growth hormone (GH) deficiency because replacement of GH or insulin-like growth factor (IGF) I, the mediator of GH action, leads to resumption of growth despite the lack of other pituitary hormones. Hypophysectomized (hypox) rats have, therefore, often been used to study metabolic consequences of GH deficiency and its effects on tissues concerned with growth. The present study was undertaken to assess the effects of hypophysectomy on the serum and pancreatic levels of the three major islet hormones insulin, glucagon, and somatostatin, as well as on IGF-I. Immunohistochemistry (IHC), in situ hybridization (ISH), radioimmunoassays (RIA), and Northern blot analysis were used to localize and quantify the hormones in the pancreas at the peptide and mRNA levels. IHC showed slightly decreased insulin levels in the ß cells of hypox compared with normal, age-matched rats whereas glucagon in a cells and somatostatin in d cells showed increase. IGF-I, which localized to a cells, showed decrease. ISH detected a slightly higher expression of insulin mRNA and markedly stronger signals for glucagon and somatostatin mRNA in the islets of hypox rats. Serum glucose concentrations did not differ between the two groups although serum insulin and C-peptide were lower and serum glucagon was higher in the hypox animals. These changes were accompanied by a more than tenfold drop in serum IGF-I. The pancreatic insulin content per gram of tissue was not significantly different in hypox and normal rats. Pancreatic glucagon and somatostatin per gram of tissue were higher in the hypox animals. The pancreatic IGF-I content of hypox rats was significantly reduced. Northern blot analysis gave a 2.6-, 4.5-, and 2.2-fold increase in pancreatic insulin, glucagon, and somatostatin mRNA levels, respectively, in hypox rats, and a 2.3-fold decrease in IGF-I mRNA levels. Our results show that the fall of serum IGF-I after hypophysectomy is accompanied by a decrease in pancreatic IGF-I peptide and mRNA but by partly discordant changes in the serum concentrations of insulin and glucagon and the islet peptide and/or mRNA content of the three major islet hormones. It appears that GH deficiency resulting in a “low IGF-I state” affects translational efficiency of these hormones as well as their secretory responses. The maintenance of normoglycemia in the presence of reduced insulin and elevated glucagon serum levels, both of which would be expected to raise blood glucose, may result mainly from the enhanced insulin sensitivity, possibly due to GH deficiency and the subsequent decrease in IGF-I production. [ABSTRACT FROM AUTHOR]

The role of human dendritic cells (DC) in the immune response toward intracellularly growing Listeria was analyzed under in vitro conditions using several morphological and functional methods. DC incubated withListeria innocuaandL. monocytogenes, respectively, readily phagocytosed the bacteria. Listeria did not impair viability and immunogenic potential of human DC. Listerial antigens were found to be processed within the lysosomal compartment of DC and colocalized with major histocompatibility complex (MHC) class II molecules, as shown by fluorescence and transmission electron microscopy. DC challenged with apathogenicL. innocuawere highly effective in priming autologous naïve T cells (mainly CD4+) in vitro. The T cells strongly proliferated in the presence of DC incubated withL. innocua, which could be significantly inhibited by anti-MHC II mAb.L. innocua-primed T cells were also successfully stimulated by DC harboring the pathogenicL. monocytogenes, either the wild-type strain EGD or the p60 reduced mutant strain RIII. From our results, we conclude that human DC infected with nonpathogenic intracellular bacteria are able to efficiently prime naïve T cells, which are then suitable for recognition of antigens derived from related virulent bacterial species. This in vitro human model provides an interesting tool for basic research in infectious immunology and possibly for a new immunotherapy. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes is the causative agent of infections like sepsis and meningitis, especially in immunocompromised hosts. Human macrophages are able to phagocytose and digest L. monocytogenes but IL-4 prevents human macrophages from killing the bacteria, the mechanisms of which are unknown. In the present study, we examined various listeria species and strains including wild-type and deletion mutants in human macrophages pretreated with IL-4. To analyse the IL-4-mediated deactivation process, we combined quantitative infection assays with various morphologic methods. IL-4 facilitates survival and escape of the pathogenic L. monocytogenes wild-type strain 10403S from the macrophage phagosomes. In untreated macrophages, the isogenic listeriolysin deletion mutant strain DP-L2161 was killed and did not escape from the phagolysosomes. However, after macrophage deactivation with IL-4 DP-L2161 survived and escaped from the phagosomes. This was also the case, but to a lesser extent, even for the naturally avirulent L. innocua. As detected by confocal laser-scanning fluorescence microscopy and electron microscopy, IL-4 permitted the escape of all listeria species tested, including DP-L2161 and L. innocua from the phagosomal compartment of the macrophages. We conclude that escape from the phagosome and survival of the listeria species tested in IL-4-deactivated human macrophages is independent of the virulence factor listeriolysin. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-alpha (TNF-α) plays an important role in liver inflammation. CD40-CD40 ligand (CD40-CD40L) is a key receptor–ligand signaling pair involved in the adaptive immune response and pathogenesis of autoimmune diseases. In mice, CD40 activation leads to sickness behavior syndrome (SBS) comprising weight loss, sleep disruption and depression, which can be blocked by administration of the TNF-inhibitor etanercept. In the present study, we assessed the extent of hepatic inflammation in mice devoid of the TNF-receptor 1 (TNFR1)-mediated signaling pathway. The TNFR1-depleted (TNFR1−/−) adult mice and their wild type littermates were given a single intra-peritoneal injection of CD40 agonist monoclonal antibody (mAb) or rat IgG2a isotope control. As described previously, TNFR1−/− mice were protected from SBS upon CD40 mAb treatment. Cd40, tnf and tnfr1 mRNA and Tnf-α peptide were increased in the liver of CD40 mAb-stimulated wild type mice. Serum alanine aminotransferase was elevated in both CD40-activated wild type and TNFR1−/− mice. TNFR1−/− mice showed much less intra-parenchymal infiltrates, hepatocellular necrosis, and perivascular clusters upon CD40 mAb activation than their wild type littermates. A gene expression microarray detected increased activity of metabolic and detoxification pathways and decreased activity of inflammatory pathways. We conclude that immune activation and development of liver inflammation in CD40L interactions depend on TNFR1-mediated signaling pathways and are counteracted by alterations in metabolic pathways. [ABSTRACT FROM AUTHOR]

The present study investigates the expression of IGF-I in the early developing tilapia (Oreochromis niloticus). IGF-I was detected very early in ontogeny (4-5 days postfertilization, DPF), first in liver and in organs involved in growth and metabolism, thus suggesting a high physiological impact of IGF-I in growth, metabolism, and organogenesis. [ABSTRACT FROM AUTHOR]