The postnatal development of the compartments in human lymph nodes up to 15 years of age.

The postnatal development of normal human lymph nodes (LN) is largely unknown but is of relevance for intranodal desensitization and for comparison to lymphoma. Superficial inguinal lymphoid (LN) of 25 children (newborn up to 14 years) were studied by routine histology and immunohistology for T and B lymphocytes. The LN were obtained from the legal medicine department at necropsy. The cortex and medulla were identifiable in LN of children of less than 1 month of age. Later high endothelial venules as typical structures for the T cell area are present. Secondary follicles were obvious from 3 months of age onwards in lymph nodes of adolescents also the histology of the LN was similar to adults. The structural elements for an intranodal desensitization are given in human children. The normal development of LN structure is essential to identify pathology like lymphoma in children.

Ceremonies of gratitude following the dissection course: A report on procedures in departments of anatomy in German speaking countries.

The departments of anatomy in Germany, Austria and the German-speaking part of Switzerland were sent comprehensive (18 items) questionnaires requesting details on memorial ceremonies held at the close of the dissection course in the medical curriculum, including objectives, organization, number of participants and the role of the medical students. The response rate was very high (95%). In more than 95% of instances a ceremony is held, initiated mainly after 1970. The titles of the ceremony range from commemoration ceremony (42%), service of mourning (19%) memorial service (19%) to ceremony of gratitude (7%). The number of participants exceeds 300 in 15% of these ceremonies. The invitation comes mostly from the student group organizing the ceremony (62%). The ceremony is offered mainly for the students of the course (23%), for student tutors (16%), relatives of the body donors (23%) and scientific staff (15%). The students actively participate with musical contributions (19%), gestures such as candles (17%) and flowers (12%), speeches (17%) and readings (12%). The relevance of the practical dissection course and body donation programs is also discussed. The results are compared to ceremonies in various countries with different religious backgrounds. This dissection course is unique among all courses in the medical curriculum as it obviously also has spiritual aspects.

[Start-up grants for young scientists in German medical universities : Can the clinical scientist be saved?] / Anschubfinanzierung für junge Wissenschaftler in der Universitätsmedizin in Deutschland : Ist der "clinical scientist" so zu retten?

BACKGROUND: German medical faculties currently have severe financial problems. There is the conflict between financing teaching medical students, inpatient and outpatient costs and supporting basic and applied research. METHODS: Young postdocs can apply for a grant to start research projects to establish techniques on publishing data as a basis for applying for grants from the German Research Foundation or foundations with a critical review system. Successful applicants from the years 1998-2011 were asked to answer a questionnaire. RESULTS: The annual number of applications ranged from 28 to 96 per year. Within the first period of our analysis ranging from 1998 to 2004, a mean number of 69.5 % ± 14.0 % of submitted grant applications were approved annually in comparison to an average approval of 30.9 % ± 11 % in the years 2006-2001. In total 353 projects were funded with a mean amount of money for a project of approximately 18,640 EUR. The mean amount of external grant money following the start-up period was 7.2 times the money initially spent. That is an excellent return of investment. There were no differences between applicants from the department of surgery or department of internal medicine. In the meantime, 56 % of men and 42 % of women have achieved the academic degree university lecturer (privatdozent). Furthermore, 71 % of the participants evaluated this start-up research as supportive for their postdoctoral qualification (habilitation). CONCLUSION: The program for initial investment for young postdocs by internal start-up grants is overall successful.

[Surgery as specialization for female physicians: Results from course evaluations and alumni studies at MHH]. / Chirurgie als Weiterbildungsfach für Ärztinnen : Ergebnisse von Lehrevaluationen und Absolventenstudien an der MHH.

BACKGROUND: There is a lack of young surgeons in Germany. In order to provide a successful learning environment in medical education and to attract more physicians, training concepts need to be regularly controlled. MATERIAL AND METHODS: Evaluation results compiled over several years from the Hanover Medical School (MHH) were analyzed for gender-related differences. In addition to overall satisfaction with practical training items were included that consider aspects of interaction between students and instructors. Furthermore, alumni studies provided data on the postgraduate specialty choice made by MHH students. OBJECTIVES: Surgical training is integrated into medical education as block training periods of various durations. Against the background of an increased percentage of women in medicine this article analyzed whether surgery is evaluated differently between female and male medical students with respect to their experiences in clinical teaching. RESULTS: Evaluations of clinical training in surgery demonstrated that female and male medical students do not differ substantially with respect to the teaching quality; however, young female physicians choose surgery as a professional option less frequently than men. CONCLUSION: A systematic review of clinical training evaluations is crucial to identify weaknesses of current curricula. More empirical data from other faculties can induce discussions about the attractiveness of surgery as a profession.

Histology and ultrastructure of the lymph nodes of the buffalo (Bos bubalus).

Pre-scapular, femoral and mesenteric lymph nodes from five buffalo calves and five buffalo bulls were studied using light and transmission electron microscopy. The nodes were surrounded with a thin capsule of dense connective tissue and smooth muscles. Subcapsular and trabecular lymphatic sinuses were lined with endothelial cells resting on a basement membrane. The cortex was formed by lymphoid follicles and inter-follicular lymphocytes. Primary and secondary follicles were observed. The medulla was made up of medullary cords of lymphocytes separated by lymphatic sinuses. These sinuses were lined with a discontinuous epithelium and interestingly crossed by reticular fibres. High endothelial venules were found in the paracortical area. Several lymphocytes were observed infiltrating the wall of these venules. The lymph nodes of the Egyptian water buffalo showed a typical structure compared with the majority of mammals, with no age-related structural variation.

Rate of tree carbon accumulation increases continuously with tree size.

Forests are major components of the global carbon cycle, providing substantial feedback to atmospheric greenhouse gas concentrations. Our ability to understand and predict changes in the forest carbon cycle--particularly net primary productivity and carbon storage--increasingly relies on models that represent biological processes across several scales of biological organization, from tree leaves to forest stands. Yet, despite advances in our understanding of productivity at the scales of leaves and stands, no consensus exists about the nature of productivity at the scale of the individual tree, in part because we lack a broad empirical assessment of whether rates of absolute tree mass growth (and thus carbon accumulation) decrease, remain constant, or increase as trees increase in size and age. Here we present a global analysis of 403 tropical and temperate tree species, showing that for most species mass growth rate increases continuously with tree size. Thus, large, old trees do not act simply as senescent carbon reservoirs but actively fix large amounts of carbon compared to smaller trees; at the extreme, a single big tree can add the same amount of carbon to the forest within a year as is contained in an entire mid-sized tree. The apparent paradoxes of individual tree growth increasing with tree size despite declining leaf-level and stand-level productivity can be explained, respectively, by increases in a tree's total leaf area that outpace declines in productivity per unit of leaf area and, among other factors, age-related reductions in population density. Our results resolve conflicting assumptions about the nature of tree growth, inform efforts to undertand and model forest carbon dynamics, and have additional implications for theories of resource allocation and plant senescence.

Expression of caveolin-1 and podocalyxin in rat lungs challenged with 2-kDa macrophage-activating lipopeptide and Flt3L.

Caveolin-1 is one of the important regulators of vascular permeability in inflamed lungs. Podocalyxin is a CD34 protein expressed on vascular endothelium and has a role in podocyte development in the kidney. Few data are available on the expression of caveolin-1 and podocalyxin in lungs challenged with Toll-like receptor 2 (TLR2) agonists such as mycoplasma-derived macrophage activating lipopeptide or with immune modulators such as Fms-like tyrosine kinase receptor-3 ligand (Flt3L), which expands dendritic cell populations in the lung. Because of the significance of pathogen-derived molecules that act through TLR2 and of the role of immune modulators in lung physiology, we examine the immunohistochemical expression of caveolin-1 and podocalyxin in lungs from rats challenged with a 2-kDa macrophage-activating lipopeptide (MALP-2) and Flt3L. Normal rat lungs expressed caveolin-1 in alveolar septa, vascular endothelium and airway epithelium, especially along the lateral borders of epithelial cells but not in alveolar macrophages. MALP-2 and Flt3L decreased and increased, respectively, the expression of caveolin-1. Caveolin-1 expression seemed to increase in microvessels in bronchiole-associated lymphoid tissue (BALT) in Flt3L-challenged lungs but not in normal or MALP-2-treated lungs. Podocalyxin was absent in the epithelium and alveolar macrophages but was present in the vasculature of control, Flt3L- and MALP-2-treated rats. Compared with control and MALP-2-treated rats, Flt3L-treated lungs showed greater expression of podocalyxin in BALT vasculature and at the interface of monocytes and the endothelium. These immunohistochemical data describing the altered expression of caveolin-1 and podocalyxin in lungs treated with MALP-2 or Flt3L encourage further mechanistic studies on the role of podocalyxin and caveolin-1 in lung inflammation.

Radiological anatomy - evaluation of integrative education in radiology.

PURPOSE: Evaluation and analysis of the integrative course "Radiological Anatomy" established since 2007 at the Medical School Hannover (MHH) in comparison with conventional education. MATERIALS AND METHODS: Anatomy and radiology are usually taught separately with a considerable time lag. Interdisciplinary teaching of these associated subjects seems logical for several reasons. Therefore, the integrative course "Radiological Anatomy" was established in the second year of medical education, combining these two closely related subjects. This interdisciplinary course was retrospectively evaluated by consideration of a student questionnaire and staff observations. The advantages and disadvantages of integrative teaching in medical education are discussed. RESULTS: The course ratings were excellent (median 1; mean 1.3 on a scale of 1 to 6). This is significantly (p < 0.001) better than the average of all evaluated courses in the respective term (grade 2.8). The course improved the anatomical comprehension (90 %) and the students stated that the topics were relevant for their future medical education (90 %). Furthermore, interest in the subject's anatomy and radiology increased during the course (88 %). According to the students' suggestions the course was enhanced by a visitation in the Department of Radiology and the additional topic central nervous system. CONCLUSION: Integrative teaching of anatomy and radiology was well received by the students. Both, anatomical and radiological comprehension and the motivation to learn were improved. However, it should be considered, that the amount of work and time required by the teaching staff is considerably increased compared to traditional teaching.

An elegant technique for ex vivo imaging in experimental research-Optical coherence tomography (OCT).

Optical coherence tomography (OCT) is an elegant technology for imaging of tissues and organs and has been established for clinical use for around a decade. Thus, it is used in vivo but can also serve as a valuable ex vivo imaging tool in experimental research. Here, a brief overview is given with a focus on an ex vivo application of OCT. Image and video examples of freshly obtained murine lungs are included. The main advantage of OCT for ex vivo analysis is the non-contact, non-invasive, and non-destructive fast acquisition of a three-dimensional data set with micrometer-resolution.

[The German academic degree "Dr. med." is better than its reputation. Results of a questionnaire of doctoral students]. / Die Promotion in der Medizin ist besser als ihr Ruf. Ergebnisse einer Befragung von Doktoranden.

BACKGROUND: Recently there were mostly emotional debates about the scientific background and relevance of the German academic title "Dr. med.", while objective data are scarce. METHODS: When submitting their doctoral thesis at the Medical School of Hannover students were asked anonymously about the type, topic, duration, quality of supervision as well as frequency and type of publication of the results. RESULTS: 180 doctoral candidates (62% women) participated in the study. The supervision was graded as good by the majority of students. The duration working on the thesis was equivalent to 47 weeks of a full time employment. There was some negative influence in participating in lectures and courses. Nearly all participants (98%) would recommend younger students to work on a dissertation as they had done themselves in parallel to the curriculum. The ability of how to interprete scientific data was assumed to be positively influenced. About two thirds stated that the results had been published in original articles at the time of submitting the thesis. CONCLUSIONS: More data from other medical faculties are needed to document the relevance of the medical dissertation to replace the emotional by a more rational debate.

Dipeptidyl peptidase IV (DPP4) deficiency increases Th1-driven allergic contact dermatitis.

BACKGROUND: CD26 or dipeptidyl peptidase IV (DPP4) is known to be involved in several immunological processes and has recently been reported to play a crucial role in the allergic responses of the lungs. OBJECTIVES: To explore the impact of DPP4 on the allergic response of the skin. METHODS: Skin biopsies from patients suffering from atopic dermatitis (AD) and healthy controls were investigated for the expression of CD26/DPP4. Furthermore, the functional impact of CD26 was investigated in two models of contact hypersensitivity using CD26/DPP4-deficient and wild-type rats. Dinitrochlorobenzene (DNCB) was used to induce a T helper type 1 (Th1)-dominated inflammation and toluene-2,3-diisocyanate for a Th2-pronounced inflammation. The inflammatory responses were determined by histological quantification, flow cytometry [fluorescence-activated cell sorting (FACS)], and an enzyme-linked immunosorbant assay (ELISA). RESULTS: CD26/DPP4-expression was up-regulated in the lesional skin biopsies of patients compared with healthy controls as well as in both models of contact hypersensitivity. However, in the more Th2-driven model, a reduced inflammatory skin response was found in CD26/DPP4-deficient rats, analogous to the effects observed recently in a rat model of asthma. In partial contrast, there was an aggravation of local skin inflammation in CD26/DPP4-deficient rats under conditions of Th1-like skin inflammation. CONCLUSION AND CLINICAL RELEVANCE: The up-regulation of CD26 in atopic dermatitis represents a new finding, which has also been seen in other inflammatory skin diseases. However, tissue expression of CD26/DPP4 in immunological skin response can either be beneficial or aggravating, depending on a possible Th1/Th2 shift. This might have consequences for humans suffering from diabetes mellitus treated by DPP4 inhibitors, who have eczematous skin diseases as a co-morbidity.

[Lymphatic tissue of the nose (NALT) and larynx (LALT) in species comparison: human, rat, mouse]. / Das lymphatische Gewebe der Nase (NALT) und des Kehlkopfes (LALT) im Speziesvergleich: Mensch, Ratte, Maus.

Nose- and larynx associated lymphatic tissues (NALT and LALT) vary markedly between humans, rats and mice. NALT of rats and mice is formed by paired lymphoid aggregates in the nasal cavity, while it consists of individual mucosa associated lymphoid follicles throughout the nose in humans. In addition to NALT, tonsils are present in humans, but not in rats and mice. In the larynx, LALT can be found in humans, but not in rats. Size and functionality of NALT, tonsils and LALT vary with age. The extrapolation of data obtained from rodents to humans should be carefully evaluated due to these differences. The term common mucosal immune system should replaced by the term "integrated" MALT and the immunological differences between respiratory and digestive tract should always be considered.

Reduced airway inflammation in CD26/DPP4-deficient F344 rats is associated with altered recruitment patterns of regulatory T cells and expression of pulmonary surfactant proteins.

INTRODUCTION: CD26 is highly expressed on lung epithelial cells as well as on immune cells. Ovalbumin (OVA)-induced airway inflammation induces a further increase of CD26 expression. CD26-deficient rat strains exhibit blunted clinical courses in models of experimental asthma. OBJECTIVE: (1) To investigate the involvement of regulatory T cells (Tregs) and the surfactant system in a rat model of genetic CD26 deficiency. (2) To investigate regulatory mechanisms dependent on the endogenous CD26 expression. (3) To investigate the impact of CD26 on surfactant protein (SP)-levels under inflammatory conditions. METHODS: Wild-type and CD26-deficient F344 rats were sensitized to and challenged with OVA. Subsequently, airway inflammation, SP levels as well as surface tension of the bronchoalveolar lavage (BAL) fluid were evaluated. RESULTS: CD26 deficiency led to decreased airway inflammation, e.g. reduced numbers of eosinophils and activated T cells in the BAL. Remarkably, the CD26-deficient rats exhibited a significantly increased influx of FoxP3(+) Tregs into the lungs and increased IL-10-secretion/production by draining lymph node cells in culture experiments. Furthermore, in OVA-challenged CD26-deficient rats, the increase of the expression of the collectins SP-A and SP-D as well as of the surface tension-active SP-B was significantly less pronounced than in the CD26-positive strain. Only in the wild-type rats, functional alterations of the surfactant system, e.g. the increased surface tension were obvious after OVA challenge. CONCLUSION: Reduced airway inflammation in CD26-deficient F344 rats appear to be mediated by differences in the recruitment and activity of Tregs. This altered inflammation is associated with differences in the SP expression as well as function.

Effects of autotransplanted lymph node fragments on the lymphatic system in the pig model.

Secondary lymphedema often develops after removal of lymph nodes in combination with radiation therapy, in particular in patients with breast cancer, inguinal cancer, cervical cancer and melanoma. No convincing treatment for the prevention and therapy of acquired lymphedema exists so far, therefore we wanted to show the reintegration of transplanted avascular lymph node fragments in the lymphatic system and positive effects of the transplanted fragments on the restoration of the lymphatic flow in this study. A total of 26 minipigs underwent lymphadenectomy of both groins. A minimum of one lymph node was retransplanted. The lymph nodes were cut into small pieces and retransplanted in the left groin (n = 17) or in both groins (n = 9). Different retransplantation techniques were investigated, transplantation of large versus small fragments, with and without capsule. The lymph flow was evaluated 5 and 8 months after surgery, using SPECT/CT and Berlin Blue. The results were confirmed by dissection. The lymph node transplants were assessed histologically. In contrast to the lymph flow in the transplanted groin, the lymph flow in the non-transplanted groin was often malfunctioning. Large lymph node fragments were found reintegrated in the lymphatic system more often than small slices of lymph node fragments. About 5 months after surgery impairment of lymph flow was seen especially after retransplantation of small slices of lymph node fragments. In seven out of eight minipigs a dermal backflow developed in the non-transplanted groin, 8 months after surgery. Only one minipig of these groups developed dermal backflow in both groins. All lymph node fragments showed an organized structure histologically. Autologous lymph node transplantation has positive effects on the regeneration of lymph vessels and restoration of lymph flow after lymphadenectomy.

Airway-specific recruitment of T cells is reduced in a CD26-deficient F344 rat substrain.

Asthma is a chronic inflammatory disease affecting the airways. Increased levels of T cells are found in the lungs after the induction of an allergic-like inflammation in rats, and flow cytometry studies have shown that these levels are reduced in CD26-deficient rats. However, the precise anatomical sites where these newly recruited T cells appear primarily are unknown. Therefore, we quantified the distribution of T cells in lung parenchyma as well as in large, medium and small airways using immunohistochemical stainings combined with morphometric analyses. The number of T cells increased after the induction of an allergic-like inflammation. However, the differences between CD26-deficient and wild-type rats were not attributable to different cell numbers in the lung parenchyma, but the medium- and large-sized bronchi revealed significantly fewer T cells in CD26-deficient rats. These sites of T cell recruitment were screened further using immunohistochemistry and quantitative real-time polymerase chain reaction with regard to two hypotheses: (i) involvement of the nervous system or (ii) expression of chemokines with properties of a T cell attractor. No topographical association was found between nerves and T cells, but a differential transcription of chemokines was revealed in bronchi and parenchyma. Thus, the site-specific recruitment of T cells appears to be a process mediated by chemokines rather than nerve-T cell interactions. In conclusion, this is the first report showing a differential site-specific recruitment of T cells to the bronchi in a CD26-deficient rat substrain during an asthma-like inflammation.

Pulmonary periarterial inflammation in fatal asthma.

BACKGROUND: To date, little information has been available about pulmonary artery pathology in asthma. The pulmonary artery supplies the distal parts of the lungs and likely represents a site of immunological reaction in allergic inflammation. The objective of this study was to describe the inflammatory cell phenotype of pulmonary artery adventitial inflammation in lung tissue from patients who died of asthma. METHODS: We quantified the different inflammatory cell types in the periarterial region of small pulmonary arteries in lung tissue from 22 patients who died of asthma [fatal asthma (FA)] and 10 control subjects. Using immunohistochemistry and image analysis, we quantified the cell density for T lymphocytes (CD3, CD4, CD8), B lymphocytes (CD20), eosinophils, mast cells (chymase and tryptase), and neutrophils in the adventitial layer of pulmonary arteries with a diameter smaller than 500 microm. RESULTS: Our data (median/interquartile range) demonstrated increased cell density of mast cells [FA=271.8 (148.7) cells/mm2; controls=177.0 (130.3) cells/mm2, P=0.026], eosinophils [FA=23.1 (58.6) cells/mm2; controls=0.0 (2.3) cells/mm2, P=0.012], and neutrophils [FA=50.4 (85.5) cells/mm2; controls=2.9 (30.5) cells/mm2, P=0.009] in the periarterial space in FA. No significant differences were found for B and T lymphocytes or CD4+ or CD8+ subsets. Chymase/tryptase positive (MCCT) mast cells predominated over tryptase (MCT) mast cells in the perivascular arterial space in both asthma patients and controls [MCCT/(MCCT+MCT)=0.91 (0-1) in FA and 0.75 (0-1) in controls, P=0.86]. CONCLUSIONS: Our results show that the adventitial layer of the pulmonary artery participates in the inflammatory process in FA, demonstrating increased infiltration of mast cells, eosinophils, and neutrophils, but not of T and B lymphocytes.

Increased surfactant protein a and d expression in acute ovalbumin-induced allergic airway inflammation in brown norway rats.

BACKGROUND: The surfactant proteins SP-A and SP-D, components of the innate immune system, are involved in host defence. OBJECTIVE: We tested the hypothesis that ovalbumin (OVA) challenge leads to an upregulation of both proteins in alveolar epithelial type II cells (AEII) and Clara cells and to an enhanced uptake by macrophages. METHODS: After sensitization with OVA and heat-killed Bordetella pertussis challenge followed intratracheally with 0.5% OVA on day 13. One day after challenge lung tissue and bronchoalveolar lavage fluid (BALF) of sensitized NaCl- and OVA-challenged Brown Norway rats were compared with home cage controls using qRt-PCR, Western blot and immunohistochemistry. RESULTS: After OVA challenge (1) eosinophils increased significantly in the BALF, (2) the total amount of SP-A and SP-D was significantly increased in lung tissue, (3) the amount of SP-A was significantly and the amount of SP-D was remarkably elevated in BALF, and (4) the levels of SP-A and SP-D mRNA in lung tissue were significantly elevated. Using quantitative immunohistochemistry, we found (5) significantly higher surface fractions of SP-A- and SP-D-labelled AEII, (6) no differences in the surface fractions of SP-A- and SP-D-labelled bronchial Clara cells, and (7) a significantly increased cell density of unlabelled and SP-A-labelled macrophages. CONCLUSIONS: Thus, combining molecular biological and histological methods we suggest that after OVA challenge (1) AEII but not Clara cells show a significantly higher expression of SP-A and SP-D leading also to higher amounts of both SPs in BALF and (2) macrophages gather predominantly SP-A.